DNA damage induced during mitosis undergoes DNA repair synthesis.

Understanding the mitotic DNA damage response (DDR) is critical to our comprehension of cancer, premature aging and developmental disorders which are marked by DNA repair deficiencies. In this study we use a micro-focused laser to induce DNA damage in selected mitotic chromosomes to study the subsequent repair response. Our findings demonstrate that (1) mitotic cells are capable of DNA repair as evidenced by DNA synthesis at damage sites, (2) Repair is attenuated when DNA-PKcs and ATM are simultaneously compromised, (3) Laser damage may permit the observation of previously undetected DDR proteins when damage is elicited by other methods in mitosis, and (4) Twenty five percent of mitotic DNA-damaged cells undergo a subsequent mitosis. Together these findings suggest that mitotic DDR is more complex than previously thought and may involve factors from multiple repair pathways that are better understood in interphase

Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures

Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4+ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions

Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study

INTRODUCTION: Severe acute renal failure (sARF) is associated with considerable morbidity, mortality and use of healthcare resources; however, its precise epidemiology and long-term outcomes have not been well described in a non-specified population. METHODS: Population-based surveillance was conducted among all adult residents of the Calgary Health Region (population 1 million) admitted to multidisciplinary and cardiovascular surgical intensive care units between May 1 1999 and April 30 2002. Clinical records were reviewed and outcome at 1 year was assessed. RESULTS: sARF occurred in 240 patients (11.0 per 100,000 population/year). Rates were highest in males and older patients (≥65 years of age). Risk factors for development of sARF included previous heart disease, stroke, pulmonary disease, diabetes mellitus, cancer, connective tissue disease, chronic renal dysfunction, and alcoholism. The annual mortality rate was 7.3 per 100,000 population with rates highest in males and those ≥65 years. The 28-day, 90-day, and 1-year case-fatality rates were 51%, 60%, and 64%, respectively. Increased Charlson co-morbidity index, presence of liver disease, higher APACHE II score, septic shock, and need for continuous renal replacement therapy were independently associated with death at 1 year. Renal recovery occurred in 78% (68/87) of survivors at 1 year. CONCLUSION: sARF is common and males, older patients, and those with underlying medical conditions are at greatest risk. Although the majority of patients with sARF will die, most survivors will become independent from renal replacement therapy within a year

Making a case for power-sensitive water modelling: a literature review

Models are widely used to research hydrological change and risk. However, the power embedded in the modelling process and outcomes is often concealed by claiming their neutrality. Our review shows that in the scientific literature relatively little attention is given to the influence of models on development processes and outcomes in water governance. At the same time, an emerging body of work offering critical insights into the political implications of hydrological models and a nuanced understanding of their application in context has begun to flourish. Drawing on this work, we call for power-sensitive modelling which includes the following considerations: take a holistic approach to modelling beyond programming and coding; foster accountability; work towards just and equitable water distributions; be transparent about the expectations and choices made; and democratise modelling by giving space to and being mindful of representations of multiple bodies of knowledge and multiple stakeholders and by incorporating marginalised people and nature into the modelling process. Our call should not be understood as a suggestion to do away with modelling altogether, but rather as an invitation to interrogate how quantitative models may help to foster transformative pathways towards more just and equitable water distributions.Volkswagen FoundationPeer Reviewe

Dynamics of HIV-1 Assembly and Release

Assembly and release of human immunodeficiency virus (HIV) occur at the plasma membrane of infected cells and are driven by the Gag polyprotein. Previous studies analyzed viral morphogenesis using biochemical methods and static images, while dynamic and kinetic information has been lacking until very recently. Using a combination of wide-field and total internal reflection fluorescence microscopy, we have investigated the assembly and release of fluorescently labeled HIV-1 at the plasma membrane of living cells with high time resolution. Gag assembled into discrete clusters corresponding to single virions. Formation of multiple particles from the same site was rarely observed. Using a photoconvertible fluorescent protein fused to Gag, we determined that assembly was nucleated preferentially by Gag molecules that had recently attached to the plasma membrane or arrived directly from the cytosol. Both membrane-bound and cytosol derived Gag polyproteins contributed to the growing bud. After their initial appearance, assembly sites accumulated at the plasma membrane of individual cells over 1–2 hours. Assembly kinetics were rapid: the number of Gag molecules at a budding site increased, following a saturating exponential with a rate constant of ∼5×10−3 s−1, corresponding to 8–9 min for 90% completion of assembly for a single virion. Release of extracellular particles was observed at ∼1,500±700 s after the onset of assembly. The ability of the virus to recruit components of the cellular ESCRT machinery or to undergo proteolytic maturation, or the absence of Vpu did not significantly alter the assembly kinetics

Decarbonising the transport and energy sectors: Technical feasibility and socioeconomic impacts in Costa Rica

Compliance with the Paris Agreement requires the transformation of national economies to meet net-zero carbon dioxide emissions by mid-century. To accomplish this, countries need to define long-term decarbonisation strategies with near- and mid-term actions to determine their ideal future scenario while maximizing socioeconomic benefits. This paper describes the process followed to support the creation of the decarbonisation pathway for the transport and energy sectors presented in Costa Rica's National Decarbonisation Plan. We discuss in detail the technological pathway of a deep-decarbonisation future that supports reaching net-zero emissions by 2050. Compared to a business-as-usual (BAU) scenario, our results show that the decarbonisation pathway can lead to emissions' reduction of 87% in the transport and energy sectors by 2050. Energy efficiency, the adoption of electromobility, modal-shift towards public transport and active mobility, as well as reduced demand due to digitalisation and teleworking, are found to be key drivers towards the deep-decarbonisation. These measures combined enable a 25% reduction of primary energy production by 2050. The results highlight that the decarbonisation scenario requires installing 4.4 GW more of renewable power plants by 2050, compared to the BAU scenario (80%). We also show that additional investments for the deep-decarbonisation are compensated with the reduced operating cost. Crucially, we found that the National Decarbonisation Plan results in a lower total discounted cost of about 35% of current Costa Rica's GDP, indicating that a deep decarbonisation is technically feasible and is coupled to socioeconomic benefits

Comparative analysis of different laser systems to study cellular responses to DNA damage in mammalian cells

Proper recognition and repair of DNA damage is critical for the cell to protect its genomic integrity. Laser microirradiation ranging in wavelength from ultraviolet A (UVA) to near-infrared (NIR) can be used to induce damage in a defined region in the cell nucleus, representing an innovative technology to effectively analyze the in vivo DNA double-strand break (DSB) damage recognition process in mammalian cells. However, the damage-inducing characteristics of the different laser systems have not been fully investigated. Here we compare the nanosecond nitrogen 337 nm UVA laser with and without bromodeoxyuridine (BrdU), the nanosecond and picosecond 532 nm green second-harmonic Nd:YAG, and the femtosecond NIR 800 nm Ti:sapphire laser with regard to the type(s) of damage and corresponding cellular responses. Crosslinking damage (without significant nucleotide excision repair factor recruitment) and single-strand breaks (with corresponding repair factor recruitment) were common among all three wavelengths. Interestingly, UVA without BrdU uniquely produced base damage and aberrant DSB responses. Furthermore, the total energy required for the threshold H2AX phosphorylation induction was found to vary between the individual laser systems. The results indicate the involvement of different damage mechanisms dictated by wavelength and pulse duration. The advantages and disadvantages of each system are discussed

Conservation of the endemic dwarf carnivores of Cozumel Island, Mexico.

Cozumel Island, Mexico, harbours two endemic species of dwarf procyonids: the Pygmy Raccoon Procyon pygmaeus and the Dwarf Coati Nasua nelsoni. Both species are Critically Endangered, and are among the world&rsquo;s most threatened Carnivora. Here we summarise the research we have been conducting on their ecology, evolution, genetics, and conservation. We also summarise the conservation initiatives we have been undertaking and promoting in order to advance the conservation of these unique species and their habitats. This effort illustrates the importance of an interdisciplinary approach in conservation science and action in maximising effectiveness. Nevertheless, the precarious status of the species make it imperative to continue and expand the work we have carried out in Cozumel to prevent two imminent global extinctions.<br /