Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
5,202
result(s) for
"Sinclair, Paul"
Sort by:
You see, I see : on the farm
\"A mother and child spend the day on the farm\"-- Provided by publisher.
Book
Disruption to the FOXO-PRDM1 axis resulting from deletions of chromosome 6 in acute lymphoblastic leukaemia
A common problem in the study of human malignancy is the elucidation of cancer driver mechanisms associated with recurrent deletion of regions containing multiple genes. Taking B-cell acute lymphoblastic leukaemia (B-ALL) and large deletions of 6q [del(6q)] as a model, we integrated analysis of functional cDNA clone tracking assays with patient genomic and transcriptomic data, to identify the transcription factors FOXO3 and PRDM1 as candidate tumour suppressor genes (TSG). Analysis of cell cycle and transcriptomic changes following overexpression of FOXO3 or PRDM1 indicated that they co-operate to promote cell cycle exit at the pre-B cell stage. FOXO1 abnormalities are absent in B-ALL, but like FOXO3, FOXO1 expression suppressed growth of TCF3::PBX1 and ETV6::RUNX1 B-ALL in-vitro. While both FOXOs induced PRDM1 and other genes contributing to late pre-B cell development, FOXO1 alone induced the key transcription factor, IRF4, and chemokine, CXCR4. CRISPR-Cas9 screening identified FOXO3 as a TSG, while FOXO1 emerged as essential for B-ALL growth. We relate this FOXO3-specific leukaemia-protective role to suppression of glycolysis based on integrated analysis of CRISPR-data and gene sets induced or suppressed by FOXO1 and FOXO3. Pan-FOXO agonist Selinexor induced the glycolysis inhibitor TXNIP and suppressed B-ALL growth at low dose (ID50 < 50 nM).
Journal Article
Justice League Rebirth deluxe edition
\"Exploding from the pages of the blockbuster DC Universe Rebirth event, this deluxe edition collects the first eleven issues of the acclaimed series and the Rebirth special that started it, all together in one hardcover volume for the first time! Superman. Batman. Wonder Woman. The Flash. Cyborg. Green Lantern. They're more than just a team of superheroes. They're the Justice League...and they're about to enter a whole new era! The Superman these incredible heroes once knew is dead, leaving an older, wiser Man of Steel from a vanished universe to take up the fight against evil. Hal Jordan, the greatest of the Green Lanterns, has taken to the stars, entrusting his place in the League to his powerful but untested young proteges, Jessica Cruz and Simon Baz. Now the Justice League must get used to these new faces and learn to work as a team once more. But they'd better do it fast. They're about to confront the biggest threats they've ever faced, from godlike machines capable of converting all life on Earth into a weapon, to a humble hacker who's ready to hit them where it hurts most.\"-- Provided by publisher.
Book
Anthropological contributions to historical ecology: 50 questions, infinite prospects
This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.
Journal Article
Achieving the impossible
Holding the moral high ground when dealing with North Korea should be easy. But President Trump has achieved the impossible. In making his ‘fire and fury’ threat to North Korea, he descended to a level normally associated with the leadership in Pyongyang. He subsequently, at the United Nations, doubled down on his threat by warning that North Korea faced total destruction. Trump’s rhetoric confirmed Kim Jong-un’s suspicions that the United States’ primary objective is regime change. This renders a nuclear deterrent all the more important in North Korean eyes. Kim has pressed on with his programme with amazing speed.
Journal Article
Lessons learned from regional training of paediatric nephrology fellows in Africa
BackgroundAccess to care for children with kidney disease is limited in less well-resourced regions of the world and paediatric nephrology (PN) workforce development with good practical skills is critical.MethodsRetrospective review of a PN training program and trainee feedback from 1999 to 2021, based at Red Cross War Memorial Children’s Hospital (RCWMCH), University of Cape Town.ResultsA regionally appropriate 1–2-year training program enrolled 38 fellows with an initial 100% return rate to their country of origin. Program funding included fellowships from the International Pediatric Nephrology Association (IPNA), International Society of Nephrology (ISN), International Society of Peritoneal Dialysis (ISPD), and the African Paediatric Fellowship Program (APFP). Fellows were trained on both in- and out-patient management of infants and children with kidney disorders. “Hands-on skills” training included examination, diagnosis and management skills, practical insertion of peritoneal dialysis catheters for management of acute kidney injury and kidney biopsies. Of 16 trainees who completed > 1 year of training, 14 (88%) successfully completed subspecialty exams and 9 (56%) completed a master’s degree with a research component. PN fellows reported that their training was appropriate and enabled them to make a difference in their respective communities.ConclusionsThis training program has successfully equipped African physicians with the requisite knowledge and skills to provide PN services in resource-constrained areas for children with kidney disease. The provision of funding from multiple organizations committed to paediatric kidney disease has contributed to the success of the program, along with the fellows’ commitment to build PN healthcare capacity in Africa.
Journal Article
SH2B3 inactivation through CN-LOH 12q is uniquely associated with B-cell precursor ALL with iAMP21 or other chromosome 21 gain
In more than 30% of B-cell precursor acute lymphoblastic leukaemia (B-ALL), chromosome 21 sequence is overrepresented through aneuploidy or structural rearrangements, exemplified by intrachromosomal amplification of chromosome 21 (iAMP21). Although frequent, the mechanisms by which these abnormalities promote B-ALL remain obscure. Intriguingly, we found copy number neutral loss of heterozygosity (CN-LOH) of 12q was recurrent in iAMP21-ALL, but never observed in B-ALL without some form of chromosome 21 gain. As a consequence of CN-LOH 12q, mutations or deletions of the adaptor protein,
SH2B3
, were converted to homozygosity. In patients without CN-LOH 12q, bi-allelic abnormalities of
SH2B3
occurred, but only in iAMP21-ALL, giving an overall incidence of 18% in this sub-type. Review of published data confirmed a tight association between overrepresentation of chromosome 21 and both CN-LOH 12q and
SH2B3
abnormalities in B-ALL. Despite relatively small patient numbers, preliminary analysis linked 12q abnormalities to poor outcome in iAMP21-ALL (
p
= 0.03). Homology modelling of a leukaemia-associated SH2 domain mutation and in vitro analysis of patient-derived xenograft cells implicated the JAK/STAT pathway as one likely target for SH2B3 tumour suppressor activity in iAMP21-ALL.
Journal Article
NEW ZEALAND’S DEFENCE RELATIONS WITH ASEAN
New Zealand’s commitment to the security and stability of South-east Asia dates back to 1949 with an initial RNZAF deployment to the region. Its defence relations with ASEAN developed through participation in the ASEAN Regional Forum, which was formed in 1994. New Zealand is also an active participant in the recently formed ASEAN Defence Ministers Plus forum. This aims to build and sustain confidence between the region’s military and civilian defence officials through developing habits of co-operation in tackling non-traditional security issues. The evolution of the ASEAN community in the years ahead should offer opportunities for New Zealand to further strengthen its relations in the defence field.
Journal Article
Planetary Stewardship in an Urbanizing World: Beyond City Limits
Cities are rapidly increasing in importance as a major factor shaping the Earth system, and therefore, must take corresponding responsibility. With currently over half the world's population, cities are supported by resources originating from primarily rural regions often located around the world far distant from the urban loci of use. The sustainability of a city can no longer be considered in isolation from the sustainability of human and natural resources it uses from proximal or distant regions, or the combined resource use and impacts of cities globally. The world's multiple and complex environmental and social challenges require interconnected solutions and coordinated governance approaches to planetary stewardship. We suggest that a key component of planetary stewardship is a global system of cities that develop sustainable processes and policies in concert with its non-urban areas. The potential for cities to cooperate as a system and with rural connectivity could increase their capacity to effect change and foster stewardship at the planetary scale and also increase their resource security.
Journal Article
The search for MH370
In the early stages of the so-far unsuccessful search for Malaysia Airlines' missing Flight MH370, gaps in international co-operation quickly became apparent, notwithstanding the welcome involvement of 27 countries in the effort. The serious implications of these gaps demand early attention to addressing possible methods of strengthening search and rescue co-operation in the Asia-Pacific region, including ratifying the proposed Search and Rescue Convention. China can now be expected to play a more significant role in regional search and rescue operations and other humanitarian missions. There is a need to engage China in the development of a regional search and rescue model.
Journal Article