Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus

A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules

Life path analysis: scaling indicates priming effects of social and habitat factors on dispersal distances

1. Movements of many animals along a life-path can be separated into repetitive ones within home ranges and transitions between home ranges. We sought relationships of social and environmental factors with initiation and distance of transition movements in 114 buzzards Buteo buteo that were marked as nestlings with long-life radio tags. 2. Ex-natal dispersal movements of 51 buzzards in autumn were longer than for 30 later in their first year and than 35 extra-natal movements between home ranges after leaving nest areas. In the second and third springs, distances moved from winter focal points by birds that paired were the same or less than for unpaired birds. No post-nuptial movement exceeded 2 km. 3. Initiation of early ex-natal dispersal was enhanced by presence of many sibs, but also by lack of worm-rich loam soils. Distances travelled were greatest for birds from small broods and with relatively little short grass-feeding habitat near the nest. Later movements were generally enhanced by the absence of loam soils and short grassland, especially with abundance of other buzzards and probable poor feeding habitats (heathland, long grass). 4. Buzzards tended to persist in their first autumn where arable land was abundant, but subsequently showed a strong tendency to move from this habitat. 5. Factors that acted most strongly in ½-km buffers round nests, or round subsequent focal points, usually promoted movement compared with factors acting at a larger scale. Strong relationships between movement distances and environmental characteristics in ½-km buffers, especially during early ex-natal dispersal, suggested that buzzards became primed by these factors to travel far. 6. Movements were also farthest for buzzards that had already moved far from their natal nests, perhaps reflecting genetic predisposition, long-term priming or poor habitat beyond the study area

Home birth and barriers to referring women with obstetric complications to hospitals: a mixed-methods study in Zahedan, southeastern Iran

<p>Abstract</p> <p>Background</p> <p>One factor that contributes to high maternal mortality in developing countries is the delayed use of Emergency Obstetric-Care (EmOC) facilities. The objective of this study was to determine the factors that hinder midwives and parturient women from using hospitals when complications occur during home birth in Sistan and Baluchestan province, Iran, where 23% of all deliveries take place in non- hospital settings.</p> <p>Methods</p> <p>In the study and data management, a mixed-methods approach was used. In the quantitative phase, we compared the existing health-sector data with World Health Organization (WHO) standards for the availability and use of EmOC services. The qualitative phase included collection and analysis of interviews with midwives and traditional birth attendants and twenty-one in-depth interviews with mothers. The data collected in this phase were managed according to the principles of qualitative data analysis.</p> <p>Results</p> <p>The findings demonstrate that three distinct factors lead to indecisiveness and delay in the use of EmOC by the midwives and mothers studied. Socio-cultural and familial reasons compel some women to choose to give birth at home and to hesitate seeking professional emergency care for delivery complications. Apprehension about being insulted by physicians, the necessity of protecting their professional integrity in front of patients and an inability to persuade their patients lead to an over-insistence by midwives on completing deliveries at the mothers' homes and a reluctance to refer their patients to hospitals. The low quality and expense of EmOC and the mothers' lack of health insurance also contribute to delays in referral.</p> <p>Conclusions</p> <p>Women who choose to give birth at home accept the risk that complications may arise. Training midwives and persuading mothers and significant others who make decisions about the value of referring women to hospitals at the onset of life-threatening complications are central factors to increasing the use of available hospitals. The hospitals must be safe, comfortable and attractive environments for parturition and should give appropriate consideration to the ethical and cultural concerns of the women. Appropriate management of financial and insurance-related issues can help midwives and mothers make a rational decision when complications arise.</p

The O/OREOS Mission - Astrobiology in Low Earth Orbit

The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small- Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cu.cm) modules: (i) a control bus, (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment, and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for micro-organisms at 3 times during the 6-month mission. We will report on the spacecraft characteristics, payload capabilities and first operational phase of the O/OREOS mission. The science and technology rationale of O/OREOS supports NASAs scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities

Statistical Techniques Complement UML When Developing Domain Models of Complex Dynamical Biosystems

Computational modelling and simulation is increasingly being used to complement traditional wet-lab techniques when investigating the mechanistic behaviours of complex biological systems. In order to ensure computational models are fit for purpose, it is essential that the abstracted view of biology captured in the computational model, is clearly and unambiguously defined within a conceptual model of the biological domain (a domain model), that acts to accurately represent the biological system and to document the functional requirements for the resultant computational model. We present a domain model of the IL-1 stimulated NF-κB signalling pathway, which unambiguously defines the spatial, temporal and stochastic requirements for our future computational model. Through the development of this model, we observe that, in isolation, UML is not sufficient for the purpose of creating a domain model, and that a number of descriptive and multivariate statistical techniques provide complementary perspectives, in particular when modelling the heterogeneity of dynamics at the single-cell level. We believe this approach of using UML to define the structure and interactions within a complex system, along with statistics to define the stochastic and dynamic nature of complex systems, is crucial for ensuring that conceptual models of complex dynamical biosystems, which are developed using UML, are fit for purpose, and unambiguously define the functional requirements for the resultant computational model

Precocious Metamorphosis in the Juvenile Hormone–Deficient Mutant of the Silkworm, Bombyx mori

Insect molting and metamorphosis are intricately governed by two hormones, ecdysteroids and juvenile hormones (JHs). JHs prevent precocious metamorphosis and allow the larva to undergo multiple rounds of molting until it attains the proper size for metamorphosis. In the silkworm, Bombyx mori, several “moltinism” mutations have been identified that exhibit variations in the number of larval molts; however, none of them have been characterized molecularly. Here we report the identification and characterization of the gene responsible for the dimolting (mod) mutant that undergoes precocious metamorphosis with fewer larval–larval molts. We show that the mod mutation results in complete loss of JHs in the larval hemolymph and that the mutant phenotype can be rescued by topical application of a JH analog. We performed positional cloning of mod and found a null mutation in the cytochrome P450 gene CYP15C1 in the mod allele. We also demonstrated that CYP15C1 is specifically expressed in the corpus allatum, an endocrine organ that synthesizes and secretes JHs. Furthermore, a biochemical experiment showed that CYP15C1 epoxidizes farnesoic acid to JH acid in a highly stereospecific manner. Precocious metamorphosis of mod larvae was rescued when the wild-type allele of CYP15C1 was expressed in transgenic mod larvae using the GAL4/UAS system. Our data therefore reveal that CYP15C1 is the gene responsible for the mod mutation and is essential for JH biosynthesis. Remarkably, precocious larval–pupal transition in mod larvae does not occur in the first or second instar, suggesting that authentic epoxidized JHs are not essential in very young larvae of B. mori. Our identification of a JH–deficient mutant in this model insect will lead to a greater understanding of the molecular basis of the hormonal control of development and metamorphosis

CRISPR-based strategies in infectious disease diagnosis and therapy

CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases.info:eu-repo/semantics/publishedVersio

Quantum criticality in ferroelectrics

Materials tuned to the neighbourhood of a zero temperature phase transition often show the emergence of novel quantum phenomena. Much of the effort to study these new effects, like the breakdown of the conventional Fermi-liquid theory of metals has been focused in narrow band electronic systems. Ferroelectric crystals provide a very different type of quantum criticality that arises purely from the crystalline lattice. In many cases the ferroelectric phase can be tuned to absolute zero using hydrostatic pressure or chemical or isotopic substitution. Close to such a zero temperature phase transition, the dielectric constant and other quantities change into radically unconventional forms due to the quantum fluctuations of the electrical polarization. The simplest ferroelectrics may form a text-book paradigm of quantum criticality in the solid-state as the difficulties found in metals due to a high density of gapless excitations on the Fermi surface are avoided. We present low temperature high precision data demonstrating these effects in pure single crystals of SrTiO3 and KTaO3. We outline a model for describing the physics of ferroelectrics close to quantum criticality and highlight the expected 1/T2 dependence of the dielectric constant measured over a wide temperature range at low temperatures. In the neighbourhood of the quantum critical point we report the emergence of a small frequency independent peak in the dielectric constant at approximately 2K in SrTiO3 and 3K in KTaO3 believed to arise from coupling to acoustic phonons. Looking ahead, we suggest that in ferroelectric materials supporting mobile charge carriers, quantum paraelectric fluctuations may mediate new effective electron-electron interactions giving rise to a number of possible states such as superconductivity.Comment: 10 pages, 4 figure