We present new upper limits on the volume-weighted neutral hydrogen fraction,
$\bar{x}_{\rm H\,\small {i}}$
, at z ∼ 5–6 derived from spectroscopy of bright quasars. The fraction of the Lyα and Lyβ ...forests that is ‘dark’ (with zero flux) provides the only model-independent upper limit on
$\bar{x}_{\rm H\,\small {i}}$
, requiring no assumptions about the physical conditions in the intergalactic medium or the quasar's unabsorbed UV continuum. In this work, we update our previous results using a larger sample (22 objects) of medium-depth (∼ few hours) spectra of high-redshift quasars obtained with the Magellan, MMT, and VLT. This significantly improves the upper bound on
$\bar{x}_{\rm H\,\small {i}}$
derived from dark pixel analysis to
$\bar{x}_{\rm H\,\small {i}}\le 0.06{+0.05 (1\sigma )}$
at z = 5.9 and
$\bar{x}_{\rm H\,\small {i}}\le 0.04{+0.05 (1\sigma )}$
at z = 5.6. These results provide robust constraints for theoretical models of reionization, and provide the strongest available evidence that reionization has completed (or is very nearly complete) by z ≈ 6.
Homologous recombination (HR) is necessary to counteract DNA replication stress. Common fragile site (CFS) loci are particularly sensitive to replication stress and undergo pathological ...rearrangements in tumors. At these loci, replication stress frequently activates DNA repair synthesis in mitosis. This mitotic DNA synthesis, termed MiDAS, requires the MUS81-EME1 endonuclease and a non-catalytic subunit of the Pol-delta complex, POLD3. Here, we examine the contribution of HR factors in promoting MiDAS in human cells. We report that RAD51 and BRCA2 are dispensable for MiDAS but are required to counteract replication stress at CFS loci during S-phase. In contrast, MiDAS is RAD52 dependent, and RAD52 is required for the timely recruitment of MUS81 and POLD3 to CFSs in early mitosis. Our results provide further mechanistic insight into MiDAS and define a specific function for human RAD52. Furthermore, selective inhibition of MiDAS may comprise a potential therapeutic strategy to sensitize cancer cells undergoing replicative stress.
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•RAD52 promotes mitotic DNA synthesis (MiDAS) following replication stress•RAD52 promotes recruitment of MUS81 and POLD3 in mitosis•RAD52 deficiency increases mitotic chromosome missegregation•Mitotic DNA synthesis occurs independently of ATR, BRCA2, and RAD51
Tumorigenesis is frequently driven by oncogene activation, which generates so-called DNA replication “stress” and instability at specific genomic loci, called common fragile sites. Bhowmick et al. show that DNA repair synthesis at fragile sites occurs in mitosis and define a role for the homologous recombination factor RAD52 in this process.
In most organisms, ABC transporters constitute one of the largest families of membrane proteins. In humans, their functions are diverse and underpin numerous key physiological processes, as well as ...being causative factors in a number of clinically relevant pathologies. Advances in our understanding of these diseases have come about through combinations of genetic and protein biochemical investigations of these transporters and the power of in vitro and in vivo investigations is helping to develop genotype-phenotype understanding. However, the importance of ABC transporter research goes far beyond human biology; microbial ABC transporters are of great interest in terms of understanding virulence and drug resistance and industrial biotechnology researchers are exploring the potential of prokaryotic ABC exporters to increase the capacity of synthetic biology systems. Plant ABC transporters play important roles in transport of hormones, xenobiotics, metals and secondary metabolites, pathogen responses and numerous aspects of development, all of which are important in the global food security area. For 3 days in Chester, this Biochemical Society Focused Meeting brought together researchers with diverse experimental approaches and with different fundamental questions, all of which are linked by the commonality of ABC transporters.
Better use of research evidence (one form of "knowledge") in health systems requires partnerships between researchers and those who contend with the real-world needs and constraints of health ...systems. Community-based participatory research (CBPR) and integrated knowledge translation (IKT) are research approaches that emphasize the importance of creating partnerships between researchers and the people for whom the research is ultimately meant to be of use ("knowledge users"). There exist poor understandings of the ways in which these approaches converge and diverge. Better understanding of the similarities and differences between CBPR and IKT will enable researchers to use these approaches appropriately and to leverage best practices and knowledge from each. The co-creation of knowledge conveys promise of significant social impacts, and further understandings of how to engage and involve knowledge users in research are needed.
We examine the histories and traditions of CBPR and IKT, as well as their points of convergence and divergence. We critically evaluate the ways in which both have the potential to contribute to the development and integration of knowledge in health systems. As distinct research traditions, the underlying drivers and rationale for CBPR and IKT have similarities and differences across the areas of motivation, social location, and ethics; nevertheless, the practices of CBPR and IKT converge upon a common aim: the co-creation of knowledge that is the result of knowledge user and researcher expertise. We argue that while CBPR and IKT both have the potential to contribute evidence to implementation science and practices for collaborative research, clarity for the purpose of the research-social change or application-is a critical feature in the selection of an appropriate collaborative approach to build knowledge.
CBPR and IKT bring distinct strengths to a common aim: to foster democratic processes in the co-creation of knowledge. As research approaches, they create opportunities to challenge assumptions about for whom, how, and what is defined as knowledge, and to develop and integrate research findings into health systems. When used appropriately, CBPR and IKT both have the potential to contribute to and advance implementation science about the conduct of collaborative health systems research.
•Contemporary review of trends/insights to established/emerging e-waste issues.•Four typical future WEEE management scenarios are identified & discussed.•Emerging concerns: stockpiling; reuse ...standards; obsolescence; IoT, space e-debris.•Key areas of concern & measures to improve WEEE management identified & recommended.•Generation & management data standardisation required alongside political solutions.
Waste electrical and electronic equipment (WEEE) comprises a globally important waste stream due to the scarcity and value of the materials that it contains; annual generation of WEEE is increasing by 3–5% per annum. The effective management of WEEE will contribute critically to progress towards (1) realisation of the United Nations’ Sustainable Development Goals, (2) a circular economy, and (3) resource efficiency. This comprehensive review paper provides a critical and contemporary examination of the current global situation of WEEE management and discusses opportunities for enhancement. Trends in WEEE generation, WEEE-related policies and legislation are exemplified in detail. Four typical future WEEE management scenarios are identified, classified and outlined. The European Community is at the forefront of WEEE management, largely due to the WEEE Directive (Directive 2012/19/EU) which sets high collection and recycling targets for Member States. WEEE generation rates are increasing in Africa though collection and recycling rates are low. WEEE-related legislation coverage is increasing in Asia (notably China and India) and in Latin America. This review highlights emerging concerns, including: stockpiling of WEEE devices; reuse standards; device obsolescence; the Internet of Things, the potential for collecting space e-debris, and emerging trends in electrical and electronic consumer goods. Key areas of concern in regard to WEEE management are identified: the partial provision of formal systems for WEEE collection and treatment at global scale; further escalation of global WEEE generation (increased ownership, and acceleration of obsolescence and redundancy); and absence of regulation and its enforcement. Measures to improve WEEE management at global scale are recommended: incorporation of circular economy principles in EEE design and production, and WEEE management, including urban mining; extension of WEEE legislation and regulation, and improved enforcement thereof; harmonisation of key terms and definitions to permit consistency and meaning in WEEE management; and improvements to regulation and recognition of the informal WEEE management sector.
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