Role of the Mitochondrial Genome During Early Development in Mice

The role of the mitochondrial genome in early development and differentiation was studied in mouse embryos cultured in vitro from the two to four cell stage to the blastocyst (about 100 cells). During this period the mitochondria undergo morphological differentiation: progressive enlargement followed by an increase in matrix density, in number of cristae, and in number of mitochondrial ribosomes. Mitochondrial ribosomal and transfer RNA synthesis occurs from the 8 to 16 cell stage on and contributes to the establishment of a mitochondrial protein-synthesizing system. Inhibition of mitochondrial RNA- and protein-synthesis by 0.1 µg/ml of ethidium bromide or 31.2 µg/ml of chloramphenicol permits essentially normal embryo development and cellular differentiation. Mitochondrial morphogenesis is also nearly normal except for the appearance of dilated and vesicular cristae in blastocyst mitochondria. Such blastocysts are capable of normal postimplantation development when transplanted into the uteri of foster mothers. Higher concentrations of these inhibitors have general toxic effects and arrest embryo development. It is concluded that mitochondrial differentiation in the early mouse embryo occurs through the progressive transformation of the preexisting mitochondria and is largely controlled by the nucleocytoplasmic system. Mitochondrial protein synthesis is required for the normal structural organization of the cristae in blastocyst mitochondria. Embryo development and cellular differentiation up to the blastocyst stage are not dependent on mitochondrial genetic activity

Report of the panel on lithospheric structure and evolution, section 3

The panel concluded that NASA can contribute to developing a refined understanding of the compositional, structural, and thermal differences between continental and oceanic lithosphere through a vigorous program in solid Earth science with the following objectives: determine the most fundamental geophysical property of the planet; determine the global gravity field to an accuracy of a few milliGals at wavelengths of 100 km or less; determine the global lithospheric magnetic field to a few nanoTeslas at a wavelength of 100 km; determine how the lithosphere has evolved to its present state via acquiring geologic remote sensing data over all the continents

Thermodynamically accurate modeling of the catalytic cycle of photosynthetic oxygen evolution: A mathematical solution to asymmetric Markov chains

AbstractForty-three years ago, Kok and coworkers introduced a phenomenological model describing period-four oscillations in O2 flash yields during photosynthetic water oxidation (WOC), which had been first reported by Joliot and coworkers. The original two-parameter Kok model was subsequently extended in its level of complexity to better simulate diverse data sets, including intact cells and isolated PSII-WOCs, but at the expense of introducing physically unrealistic assumptions necessary to enable numerical solutions. To date, analytical solutions have been found only for symmetric Kok models (inefficiencies are equally probable for all intermediates, called “S-states”). However, it is widely accepted that S-state reaction steps are not identical and some are not reversible (by thermodynamic restraints) thereby causing asymmetric cycles. We have developed a mathematically more rigorous foundation that eliminates unphysical assumptions known to be in conflict with experiments and adopts a new experimental constraint on solutions. This new algorithm termed STEAMM for S-state Transition Eigenvalues of Asymmetric Markov Models enables solutions to models having fewer adjustable parameters and uses automated fitting to experimental data sets, yielding higher accuracy and precision than the classic Kok or extended Kok models. This new tool provides a general mathematical framework for analyzing damped oscillations arising from any cycle period using any appropriate Markov model, regardless of symmetry. We illustrate applications of STEAMM that better describe the intrinsic inefficiencies for photon-to-charge conversion within PSII-WOCs that are responsible for damped period-four and period-two oscillations of flash O2 yields across diverse species, while using simpler Markov models free from unrealistic assumptions

Metastatic Squamous Cell Carcinoma: A Cautionary Tale

Cutaneous squamous cell carcinoma (cSCC) typically arises from a malignant proliferation of keratinocytes. It is the second most common cancer in the United States and typically affects older white men. Risk factors for cSCC include ultraviolet radiation exposure, light skin tone, and immunosuppression. Although metastasis in cSCC is rare, primary tumor characteristics such as location, size, and depth of invasion, among others, can help risk-stratify lesions for local recurrence, metastatic events, and death. We present a case of primary cutaneous metastatic squamous cell carcinoma masquerading as a cyst on the left temple of a 73-year-old Caucasian man following numerous treatments of cryotherapy to an ipsilateral helical lesion

The recovery of plant community composition following passive restoration across spatial scales

Human impacts have led to dramatic biodiversity change which can be highly scale-dependent across space and time. A primary means to manage these changes is via passive (here, the removal of disturbance) or active (management interventions) ecological restoration. The recovery of biodiversity, following the removal of disturbance, is often incomplete relative to some kind of reference target. The magnitude of recovery of ecological systems following disturbance depends on the landscape matrix and many contingent factors. Inferences about recovery after disturbance and biodiversity change depend on the temporal and spatial scales at which biodiversity is measured. We measured the recovery of biodiversity and species composition over 33 years in 17 temperate grasslands abandoned after agriculture at different points in time, collectively forming a chronosequence since abandonment from 1 to 80 years. We compare these abandoned sites with known agricultural land-use histories to never-disturbed sites as relative benchmarks. We specifically measured aspects of diversity at the local plot-scale (α-scale, 0.5 m2) and site-scale (γ-scale, 10 m2), as well as the within-site heterogeneity (β-diversity) and among-site variation in species composition (turnover and nestedness). At our α-scale, sites recovering after agricultural abandonment only had 70% of the plant species richness (and ~30% of the evenness), compared to never-ploughed sites. Within-site β-diversity recovered following agricultural abandonment to around 90% after 80 years. This effect, however, was not enough to lead to recovery at our γ-scale. Richness in recovering sites was ~65% of that in remnant never-ploughed sites. The presence of species characteristic of the never-disturbed sites increased in the recovering sites through time. Forb and legume cover declines in years since abandonment, relative to graminoid cover across sites. Synthesis. We found that, during the 80 years after agricultural abandonment, old fields did not recover to the level of biodiversity in remnant never-ploughed sites at any scale. β-diversity recovered more than α-scale or γ-scale. Plant species composition recovered, but not completely, over time, and some species groups increased their cover more than others. Patterns of ecological recovery in degraded ecosystems across space and long time-scales can inform targeted active restoration interventions and perhaps, lead to better outcomes

Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations

Making the user more efficient: Design for sustainable behaviour

User behaviour is a significant determinant of a product’s environmental impact; while engineering advances permit increased efficiency of product operation, the user’s decisions and habits ultimately have a major effect on the energy or other resources used by the product. There is thus a need to change users’ behaviour. A range of design techniques developed in diverse contexts suggest opportunities for engineers, designers and other stakeholders working in the field of sustainable innovation to affect users’ behaviour at the point of interaction with the product or system, in effect ‘making the user more efficient’. Approaches to changing users’ behaviour from a number of fields are reviewed and discussed, including: strategic design of affordances and behaviour-shaping constraints to control or affect energyor other resource-using interactions; the use of different kinds of feedback and persuasive technology techniques to encourage or guide users to reduce their environmental impact; and context-based systems which use feedback to adjust their behaviour to run at optimum efficiency and reduce the opportunity for user-affected inefficiency. Example implementations in the sustainable engineering and ecodesign field are suggested and discussed

Modeling Progressive Fibrosis with Pluripotent Stem Cells Identifies an Anti-fibrotic Small Molecule.

Progressive organ fibrosis accounts for one-third of all deaths worldwide, yet preclinical models that mimic the complex, progressive nature of the disease are lacking, and hence, there are no curative therapies. Progressive fibrosis across organs shares common cellular and molecular pathways involving chronic injury, inflammation, and aberrant repair resulting in deposition of extracellular matrix, organ remodeling, and ultimately organ failure. We describe the generation and characterization of an in vitro progressive fibrosis model that uses cell types derived from induced pluripotent stem cells. Our model produces endogenous activated transforming growth factor β (TGF-β) and contains activated fibroblastic aggregates that progressively increase in size and stiffness with activation of known fibrotic molecular and cellular changes. We used this model as a phenotypic drug discovery platform for modulators of fibrosis. We validated this platform by identifying a compound that promotes resolution of fibrosis in in vivo and ex vivo models of ocular and lung fibrosis