Links between topography, wind, deflation, lakes and dust: The case of the Bodélé Depression, Chad

The Bodélé Depression, Chad is the planet's largest single source of dust. Deflation from the Bodélé could be seen as a simple coincidence of two key prerequisites: strong surface winds and a large source of suitable sediment. But here we hypothesise that long term links between topography, winds, deflation and dust ensure the maintenance of the dust source such that these two apparently coincidental key ingredients are connected by land-atmosphere processes with topography acting as the overall controlling agent. We use a variety of observational and numerical techniques, including a regional climate model, to show that: 1) contemporary deflation from the Bodélé is delineated by topography and a surface wind stress maximum; 2) the Tibesti and Ennedi mountains play a key role in the generation of the erosive winds in the form of the Bodélé Low Level Jet (LLJ); 3) enhanced deflation from a stronger Bodélé LLJ during drier phases, for example, the Last Glacial Maximum, was probably sufficient to create the shallow lake in which diatoms lived during wetter phases, such as the Holocene pluvial. Winds may therefore have helped to create the depression in which erodible diatom material accumulated. Instead of a simple coincidence of nature, dust from the world's largest source may result from the operation of long term processes on paleo timescales which have led to ideal conditions for dust generation in the world's largest dust source. Similar processes plausibly operate in other dust hotspots in topographic depressions

SWI/SNF regulates a transcriptional programme that induces senescence to prevent liver cancer

Oncogene-induced senescence (OIS) is a potent tumour suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumours. ARID1B controls p16INK4a and p21CIP1a transcription but also regulates DNA damage, oxidative stress and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence. To systematically identify SWI/SNF targets regulating senescence, we carried out a focused shRNA screen. We discovered several new senescence regulators including ENTPD7, an enzyme that hydrolyses nucleotides. ENTPD7 affects oxidative stress, DNA damage and senescence. Importantly, expression of ENTPD7 or inhibition of nucleotide synthesis in ARID1B-depleted cells results in re-establishment of senescence. Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that pro-senescence therapies could be employed against SWI/SNF-mutated cancers

The role of eastern Siberian snow and soil moisture anomalies in quasi-biennial persistence of the Arctic and North Atlantic Oscillations

 Variations in the Arctic Oscillation (AO) and its regional manifestation, the North Atlantic Oscillation (NAO), generate much of the nonseasonal variability in the winter climate over the Northern Hemisphere midlatitudes. Despite being an internal mode of the atmosphere, the Arctic and North Atlantic Oscillations (N/AO) exhibit a slightly red spectrum, varying on quasi-biennial (2–3 years) and quasi-decadal time scales. Such low-frequency variability is likely due to the coupling of the atmosphere to boundary conditions and/or external forcings. Here we show that Eurasian snow cover, particularly over eastern Siberia (ESB), exhibits quasi-biennial persistence similar to the N/AO. Furthermore, the snow-AO mechanism operates on quasi-biennial timescales, with fall ESB snow cover significantly related to vertically propagating Rossby wave activity and the N/AO for the next two to three winters. On the basis of land surface model simulations from the Global Land Data Assimilation System (GLDAS), the interseasonal carryover of ESB snow is related to soil moisture anomalies and an evaporation-convection feedback. These findings suggest quasi-biennial persistence of the N/AO is partly due to land surface forcing in the form of both ESB snow and soil moisture anomalies

The Impact of Boreal Forest Fire on Climate Warming

We report measurements and analysis of a boreal forest fire, integrating the effects of greenhouse gases, aerosols, black carbon deposition on snow and sea ice, and postfire changes in surface albedo. The net effect of all agents was to increase radiative forcing during the first year (34 ± 31 Watts per square meter of burned area), but to decrease radiative forcing when averaged over an 80-year fire cycle (–2.3 ± 2.2 Watts per square meter) because multidecadal increases in surface albedo had a larger impact than fire-emitted greenhouse gases. This result implies that future increases in boreal fire may not accelerate climate warming

A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions

The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a "two-hit" mechanismin the process of tumor-suppressor gene (TSG) inactivation. Using a murine model system of hepatocellular carcinoma (HCC) and in vivo RNAi, we test an alternative hypothesis, that such deletions can arise from selective pressure to attenuate the activity of multiple genes. By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. In addition, in human HCC patients, the combined down-regulation of functionally validated 8p TSGs is associated with poor survival, in contrast to the down-regulation of any individual gene. Our data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events

In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression

April 1, 2010Mouse models have markedly improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic experimentation. Here, we report the adaptation of loss-of-function screening to mouse models of cancer. Specifically, we have been able to introduce a library of shRNAs into individual mice using transplantable Eμ-myc lymphoma cells. This approach has allowed us to screen nearly 1,000 genetic alterations in the context of a single tumor-bearing mouse. These experiments have identified a central role for regulators of actin dynamics and cell motility in lymphoma cell homeostasis in vivo. Validation experiments confirmed that these proteins represent bona fide lymphoma drug targets. Additionally, suppression of two of these targets, Rac2 and twinfilin, potentiated the action of the front-line chemotherapeutic vincristine, suggesting a critical relationship between cell motility and tumor relapse in hematopoietic malignancies.National Institutes of Health (U.S.) (RO1 CA128803-01)Massachusetts Institute of Technology. Dept. of Biology (Training Grant)Massachusetts Institute of Technology. Undergraduate Research Opportunities ProgramNational Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant 1-U54-CA112967

The role of mobile health technologies in promoting COVID-19 prevention

Background: Researchers have found innovative ways of using mobile health (mHealth) technologies to prevent the spread of coronavirus disease 2019 (COVID-19). However, fewer studies have been done to determine their adoption and effectiveness. Objective: This review summarises the published evidence on the effect of mHealth technologies on the adoption of COVID-19 preventive measures, prevention knowledge acquisition and risk perception as well as technology adoption features for COVID-19 prevention. Methods: PubMed, IEEE and Google Scholar databases were searched for peer-reviewed literature from 1 January 2020 to 31 March 2022 for studies that evaluated the effect of mHealth technologies on COVID-19 preventive measures adoption, prevention knowledge acquisition and risk perception. Thirteen studies met the inclusion criteria and were included in this review. All the included studies were checked for quality using the mHealth evidence reporting and assessment (mERA) checklist. Results: The review found out that the utilisation of mHealth interventions such as alert text messages, tracing apps and social media platforms was associated with adherence behaviour such as wearing masks, washing hands and using sanitisers, maintaining social distance and avoiding crowded places. The use of contact tracing was linked to low-risk perception as users considered themselves well informed about their status and less likely to pose transmission risks compared to non-users. Privacy and security issues, message personalisation and frequency, technical issues and trust concerns were identified as technology adoption features that influence the use of mHealth technologies for promoting COVID-19 prevention. Conclusion: Utilisation of mHealth may be a feasible and effective way to prevent the spread of COVID-19. However, the small study samples and short study periods prevent generalisation of the findings and calls for larger, longitudinal studies that encompass diverse study settings.Peer Reviewe

Comparative Oncogenomic Analysis of Copy Number Alterations in Human and Zebrafish Tumors Enables Cancer Driver Discovery

The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs) are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs). Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.Kathy and Curt Marble Cancer Research FundArthur C. MerrillNational Institutes of Health (U.S.) (Grant CA106416)National Institutes of Health (U.S.) (Grant ROI RR020833)National Institutes of Health (U.S.) (Grant 1F32GM095213-01