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The ability to synthesize and assemble functional nanomaterials using proteins and peptides is an area of active research, merging various methodologies common in biochemistry and molecular biology to create a wide range of nanoscale materials with intriguing properties. These “bioenabled” nanomaterials have distinct advantages over their nonbiological counterparts, including diverse/precise chemical functionalization, benign aqueous-based processing conditions, and the inherent high specificity for targeted substrates. In parallel, the advent of synthetic biology is providing avenues to engineer novel protein chemistry and functionality, leading to commercialization in the startup sector. In this article, we provide a prospective review for fusing established methods in protein-enabled nanomaterials with those found commonly in synthetic biology. We first summarize significant findings and outcomes from the peptide and protein-enabled nanomaterials literature. The application of synthetic biology methodologies toward research areas of tangential similarity will also be summarized, including the directed evolution of enzymes for bioinorganic reactions, noncanonical amino acid engineering in proteins, and the incorporation of electrical active elements into anisotropic proteins. To conclude, we will suggest avenues for new research directions for protein-enabled nanomaterials that fully exploit the power of synthetic biology.
Carbapenem-resistant Enterobacterales (CRE) are common causes of healthcare-associated infections and are often multidrug resistant with limited therapeutic options. Additionally, CRE can spread within and between healthcare facilities, amplifying potential harms.
To better understand the burden, risk factors, and source of acquisition of carbapenemase genes in clinical Escherichia coli and Klebsiella spp isolates from patients in Washington to guide prevention efforts.
Multicenter prospective surveillance study.
Escherichia coli and Klebsiella spp isolates meeting the Washington state CRE surveillance case definition were solicited from clinical laboratories and tested at Washington Public Health Laboratories using polymerase chain reaction (PCR) for the 5 most common carbapenemase genes: blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48. Case patients positive by PCR were investigated by the public health department.
From October 2012 through December 2017, 363 carbapenem-resistant E. coli and Klebsiella spp isolates were tested. Overall, 45 of 115 carbapenem-resistant K. pneumoniae (39%), 1 of 8 K. oxytoca (12.5%), and 28 of 239 carbapenem-resistant E. coli (11.7%) were carbapenemase positive. Of 74 carbapenemase-positive isolates, blaKPC was most common (47%), followed by blaNDM (30%), blaOXA-48 (22%), and blaIMP (1%). Although all cases had healthcare exposure, blaKPC acquisition was associated with US health care, whereas non-blaKPC acquisition was associated with international health care or travel.
We report that blaKPC, the most prevalent carbapenemase in the United States, accounts for nearly half of carbapenemase cases in Washington state and that most KPC-cases are likely acquired through in-state health care.
In recent years, the discovery of massive quasars at
has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
Effective treatment of maternal antenatal depression may ameliorate adverse neurodevelopmental outcomes in offspring. We performed two follow-up rounds of children at age 2 and age 5 whose mothers had received either specialized cognitive-behavioural therapy or routine care for depression while pregnant. Of the original cohort of 54 women, renewed consent was given by 28 women for 2-year follow-up and by 24 women for 5-year follow-up. Child assessments at the 2-year follow-up included the Parenting Stress Index (PSI), Bayley Scales of Infant Development (BSID-III) and the Child Behaviour Checklist (CBCL). The 5-year follow-up included the Wechsler Preschool and Primary Scales of Intelligence (WPPSI-III) and again the CBCL. Treatment during pregnancy showed significant benefits for children’s development at age 2, but not at age 5. At 2 years, intervention effects were found with lower scores on the PSI Total score, Parent Domain and Child domain (d=1.44, 1.47, 0.96 respectively). A non-significant trend favoured the intervention group on most subscales of the CBCL and the BSID-III (most notably motor development: d =0.52). In contrast, at 5-year follow-up, no intervention effects were found. Also, irrespective of treatment allocation, higher depression or anxiety during pregnancy was associated with higher CBCL and lower WPPSI-III scores at 5 years. This is one of the first controlled studies to evaluate the long-term effect of antenatal depression treatment on infant neurodevelopmental outcomes, showing some benefit. Nevertheless, caution should be taken interpreting the results because of a small sample size, and larger studies are warranted.
We present Phantom, a fast, parallel, modular, and low-memory smoothed particle hydrodynamics and magnetohydrodynamics code developed over the last decade for astrophysical applications in three dimensions. The code has been developed with a focus on stellar, galactic, planetary, and high energy astrophysics, and has already been used widely for studies of accretion discs and turbulence, from the birth of planets to how black holes accrete. Here we describe and test the core algorithms as well as modules for magnetohydrodynamics, self-gravity, sink particles, dust–gas mixtures, H2 chemistry, physical viscosity, external forces including numerous galactic potentials, Lense–Thirring precession, Poynting–Robertson drag, and stochastic turbulent driving. Phantom is hereby made publicly available.
There is clear evidence that the mother's stress, anxiety, or depression during pregnancy can alter the development of her fetus and her child, with an increased risk for later psychopathology. We are starting to understand some of the underlying mechanisms including the role of the placenta, gene–environment interactions, epigenetics, and specific systems including the hypothalamic–pituitary–adrenal axis and cytokines. In this review we also consider how these effects may be different, and potentially exacerbated, in different parts of the world. There can be many reasons for elevated prenatal stress, as in communities at war. There may be raised pregnancy-specific anxiety with high levels of maternal and infant death. There can be raised interpersonal violence (in Afghanistan 90.2% of women thought that “wife beating” was justified compared with 2.0% in Argentina). There may be interactions with nutritional deficiencies or with extremes of temperature. Prenatal stress alters the microbiome, and this can differ in different countries. Genetic differences in different ethnic groups may make some more vulnerable or more resilient to the effects of prenatal stress on child neurodevelopment. Most research on these questions has been in predominantly Caucasian samples from high-income countries. It is now time to understand more about prenatal stress and psychopathology, and the role of both social and biological differences, in the rest of the world.
The importance of parasites as a selective force in host evolution is a topic of current interest. However, short-term ecological studies of host–parasite systems, on which such studies are usually based, provide only snap-shots of what may be dynamic systems. We report here on four surveys, carried out over a period of 12 years, of helminths of spiny mice (Acomys dimidiatus), the numerically dominant rodents inhabiting dry montane wadis in the Sinai Peninsula. With host age (age-dependent effects on prevalence and abundance were prominent) and sex (female bias in abundance in helminth diversity and in several taxa including Cestoda) taken into consideration, we focus on the relative importance of temporal and spatial effects on helminth infracommunities. We show that site of capture is the major determinant of prevalence and abundance of species (and higher taxa) contributing to helminth community structure, the only exceptions being Streptopharaus spp. and Dentostomella kuntzi. We provide evidence that most (notably the Spiruroidea, Protospirura muricola, Mastophorus muris and Gongylonema aegypti, but with exceptions among the Oxyuroidae, e.g. Syphacia minuta), show elements of temporal-site stability, with a rank order of measures among sites remaining similar over successive surveys. Hence, there are some elements of predictability in these systems.
Recent findings highlight that there are prenatal risks for affective disorders that are mediated by glucocorticoid mechanisms, and may be specific to females. There is also evidence of sex differences in prenatal programming mechanisms and developmental psychopathology, whereby effects are in opposite directions in males and females. As birth weight is a risk for affective disorders, we sought to investigate whether maternal prenatal cortisol may have sex-specific effects on fetal growth. Participants were 241 mothers selected from the Wirral Child Health and Development Study (WCHADS) cohort (n=1233) using a psychosocial risk stratifier, so that responses could be weighted back to the general population. Mothers provided saliva samples, which were assayed for cortisol, at home over 2 days at 32 weeks gestation (on waking, 30-min post-waking and during the evening). Measures of infant birth weight (corrected for gestational age) were taken from hospital records. General population estimates of associations between variables were obtained using inverse probability weights. Maternal log of the area under the curve cortisol predicted infant birth weight in a sex-dependent manner (interaction term P=0.029). There was a positive and statistically significant association between prenatal cortisol in males, and a negative association in females that was not statistically significant. A sex interaction in the same direction was evident when using the waking (P=0.015), and 30-min post-waking (P=0.013) cortisol, but not the evening measure. There was no interaction between prenatal cortisol and sex to predict gestational age. Our findings add to an emerging literature that suggests that there may be sex-specific mechanisms that underpin fetal programming.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
On 27 April 2015, Washington health authorities identified Escherichia coli O157:H7 infections associated with dairy education school field trips held in a barn 20–24 April. Investigation objectives were to determine the magnitude of the outbreak, identify the source of infection, prevent secondary illness transmission and develop recommendations to prevent future outbreaks. Case-finding, hypothesis generating interviews, environmental site visits and a case–control study were conducted. Parents and children were interviewed regarding event activities. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Environmental testing was conducted in the barn; isolates were compared to patient isolates using pulsed-field gel electrophoresis (PFGE). Sixty people were ill, 11 (18%) were hospitalised and six (10%) developed haemolytic uremic syndrome. Ill people ranged in age from <1 year to 47 years (median: 7), and 20 (33%) were female. Twenty-seven case-patients and 88 controls were enrolled in the case–control study. Among first-grade students, handwashing (i.e. soap and water, or hand sanitiser) before lunch was protective (adjusted OR 0.13; 95% CI 0.02–0.88, P = 0.04). Barn samples yielded E. coli O157:H7 with PFGE patterns indistinguishable from patient isolates. This investigation provided epidemiological, laboratory and environmental evidence for a large outbreak of E. coli O157:H7 infections from exposure to a contaminated barn. The investigation highlights the often overlooked risk of infection through exposure to animal environments as well as the importance of handwashing for disease prevention. Increased education and encouragement of infection prevention measures, such as handwashing, can prevent illness.
Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression.
A diagnosis of depression during pregnancy was recorded from Manchester cohort participants’ medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression.
In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively).
This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.
Evolutionary developmental biology (evo-devo) involves the integration of developmental genetics, phylogenetics and morphology in order to understand how the diversity of life evolved. The origin of developmental processes and their subsequent modifications underlie the plasticity necessary to generate novel features and patterns, which in turn underpin species diversification. Interdisciplinary cohesion between systematic and developmental fields for the study of morphological evolution remains at best patchy. An integrated approach is necessary to understand the genetic basis of developmental traits and their evolutionary significance within a phylogenetic framework. The wealth of opportunity that NGS can provide for systematics and evo-devo offers a timely opportunity to further integrate these fields.
Here, we discuss how NGS can be utilized to address several aspects of plant biology, revolutionizing both the systematic study of species and the genetic basis of the developmental traits that they exhibit. We use the South African daisy Gorteria diffusa Thunb. (Asteraceae) to illustrate the potential of a systematic evo-devo approach to study petal spot development and also discuss the importance of considering homology when generating comparative sequence datasets, as well as related topics.
Integrating systematic and evo-devo studies using NGS
Evo-devo has much to offer systematics because it can provide developmental and functional contexts for traits whose homologies are difficult to assess on the basis of morphology. More fundamentally, it also provides a perspective for understanding evolutionary processes. Plant evo-devo should be a synthesis between developmental genetics, comparative morphology and phylogenetic systematics (Hawkins 2002). Such a synthesis of fields can provide a deeper understanding of traits, illuminating the genetic basis of development and morphology within an evolutionary framework. The data to reconstruct phylogenies have never been more readily available and will become increasingly so with the continuing development of NGS technologies.
However, in practical terms, systematic and developmental fields have not been widely integrated, particularly with regard to the use of phylogenetic estimates for evo-devo studies, which, by definition, should incorporate a phylogenetic context to address the formation and modification of developmental processes and networks. Phylogenetic systematics and comparative morphology provide an optimal basis for sampling strategies and the design of developmental genetic studies. Both broad sampling and rigorous testing of a phylogenetic framework are essential to identify gene sequence homology and reconstruct ancestral states.
This study investigated whether patients who remain symptomatic more than a year following idiopathic facial paralysis gain benefit from tailored facial physiotherapy.
A two-year retrospective review was conducted of all symptomatic patients. Data collected included: age, gender, duration of symptoms, Sunnybrook facial grading system scores pre-treatment and at last visit, and duration of treatment.
The study comprised 22 patients (with a mean age of 50.5 years (range, 22–75 years)) who had been symptomatic for more than a year following idiopathic facial paralysis. The mean duration of symptoms was 45 months (range, 12–240 months). The mean duration of follow up was 10.4 months (range, 2–36 months). Prior to treatment, the mean Sunnybrook facial grading system score was 59 (standard deviation = 3.5); this had increased to 83 (standard deviation = 2.7) at the last visit, with an average improvement in score of 23 (standard deviation = 2.9). This increase was significant (p < 0.001).
Tailored facial therapy can improve facial grading scores in patients who remain symptomatic for prolonged periods.
Multiple behavioral and health outcomes, including internalizing symptoms, may be predicted from prenatal maternal anxiety, depression, or stress. However, not all children are affected, and those that are can be affected in different ways. Here we test the hypothesis that the effects of prenatal anxiety are moderated by genetic variation in the child's brain-derived neurotrophic factor (BDNF) gene, using the Avon Longitudinal Study of Parents and Children population cohort. Internalizing symptoms were assessed from 4 to 13 years of age using the Strengths and Difficulties Questionnaire (n = 8,584); a clinical interview with the adolescents was conducted at age 15 years (n = 4,704). Obstetric and psychosocial risk and postnatal maternal symptoms were included as covariates. Results show that prenatal maternal anxiety predicted internalizing symptoms, including with the diagnostic assessment at 15 years. There was a main effect of two BDNF polymorphisms (rs6265 [val66met] and rs11030104) on internalizing symptoms up to age 13. There was also genetic moderation of the prenatal anxiety effect by different BDNF polymorphisms (rs11030121 and rs7124442), although significant effects were limited to preadolescence. The findings suggest a role for BDNF gene–environment interactions in individual vulnerability to the effects of prenatal anxiety on child internalizing symptoms.
Developmental or fetal programming has emerged as a major model for understanding the early and persisting effects of prenatal exposures on the health and development of the child and adult. We leverage the power of a 14-year prospective study to examine the persisting effects of prenatal anxiety, a key candidate in the developmental programming model, on symptoms of behavioral and emotional problems across five occasions of measurement from age 4 to 13 years. The study is based on the Avon Longitudinal Study of Parents and Children cohort, a prospective, longitudinal study of a large community sample in the west of England (n = 7,944). Potential confounders included psychosocial and obstetric risk, postnatal maternal mood, paternal pre- and postnatal mood, and parenting. Results indicated that maternal prenatal anxiety predicted persistently higher behavioral and emotional symptoms across childhood with no diminishment of effect into adolescence. Elevated prenatal anxiety (top 15%) was associated with a twofold increase in risk of a probable child mental disorder, 12.31% compared with 6.83%, after allowing for confounders. Results were similar with prenatal depression. These analyses provide some of the strongest evidence to date that prenatal maternal mood has a direct and persisting effect on her child's psychiatric symptoms and support an in utero programming hypothesis.
Some studies have found an association between elevated cortisol and
subsequent depression, but findings are inconsistent. The cortisol
awakening response may be a more stable measure of
hypothalamic–pituitary–adrenal function and potentially of stress
To investigate whether salivary cortisol, particularly the cortisol
awakening response, is associated with subsequent depression in a large
Young people (aged 15 years, n = 841) from the Avon
Longitudinal Study of Parents and Children (ALSPAC) collected salivary
cortisol at four time points for 3 school days. Logistic regression was
used to calculate odds ratios for developing depression meeting ICD-10
criteria at 18 years.
We found no evidence for an association between salivary cortisol and
subsequent depression. Odds ratios for the cortisol awakening response
were 1.24 per standard deviation (95% CI 0.93–1.66, P =
0.14) before and 1.12 (95% CI 0.73–1.72, P = 0.61) after
adjustment for confounding factors. There was no evidence that the other
cortisol measures, including cortisol at each time point, diurnal drop
and area under the curve, were associated with subsequent depression.
Our findings do not support the hypothesis that elevated salivary
cortisol increases the short-term risk of subsequent depressive illness.
The results suggest that if an association does exist, it is small and
unlikely to be of clinical significance.
Although the environmental benefits of recycling plastics are well established and most geographic locations within the U.S. offer some plastic recycling, recycling rates are often low. Low recycling rates are often observed in conventional centralized recycling plants due to the challenge of collection and transportation for high-volume low-weight polymers. The recycling rates decline further when low population density, rural and relatively isolated communities are investigated because of the distance to recycling centers makes recycling difficult and both economically and energetically inefficient. The recent development of a class of open source hardware tools (e.g. RecycleBots) able to convert post-consumer plastic waste to polymer filament for 3-D printing offer a means to increase recycling rates by enabling distributed recycling. In addition, to reducing the amount of plastic disposed of in landfills, distributed recycling may also provide low-income families a means to supplement their income with domestic production of small plastic goods. This study investigates the environmental impacts of polymer recycling. A life-cycle analysis (LCA) for centralized plastic recycling is compared to the implementation of distributed recycling in rural areas. Environmental impact of both recycling scenarios is quantified in terms of energy use per unit mass of recycled plastic. A sensitivity analysis is used to determine the environmental impacts of both systems as a function of distance to recycling centers. The results of this LCA study indicate that distributed recycling of HDPE for rural regions is energetically favorable to either using virgin resin or conventional recycling processes. This study indicates that the technical progress in solar photovoltaic devices, open-source 3-D printing and polymer filament extrusion have made distributed polymer recycling and upcycling technically viable.
Literature comparing the quality of care on psychiatric intensive care units and acute wards is sparse, but a review has found differences in key areas e.g. violence, drugs and alcohol.
This study compares the response to questionnaires completed by patients, carers and qualified nursing staff from PICUs and acute wards as part of the Accreditation for Inpatient Mental Health Services (AIMS) process.
There were few differences between the standards of care on PICUs and acute wards according to patients, carers and qualified nurses. Patients reported a more negative experience of care on PICUs than trained nurses, and in particular rated low standards on accessing records and counselling. Carers reported inadequate involvement in risk assessment an assessment of their needs. Nurses generally gave positive views of standards of care.
The challenging environment of the PICU does not appear to be compromising quality of care. There is however still room for improvement for both acute wards and PICUs in key areas, including full involvement of patients and carers and imparting information.