An Overview of Physical Risks in the Mt. Everest Region

In April and May 2019, as part of National Geographic and Rolex's Perpetual Planet Everest Expedition, an interdisciplinary scientific effort conducted a suite of research on the mountain and recognized many changing dynamics, including emergent risks resulting from natural and anthropogenic changes to the biological system. In this paper, the diverse research teams highlight risks to ecosystem and human health, geologic hazards, and changing climbing conditions that may affect the local community, climbers, and trekkers in the future. This Primer brings together perspectives from across the atmospheric, biological, geological, and health sciences to better understand emergent risks on Mt. Everest and in the Khumbu region. Understanding these risks is critical for the ~10,000 people living in the Khumbu region, the thousands of visiting trekkers, and the hundreds of climbers who attempt to summit each year

A Microhomology-Mediated Break-Induced Replication Model for the Origin of Human Copy Number Variation

Chromosome structural changes with nonrecurrent endpoints associated with genomic disorders offer windows into the mechanism of origin of copy number variation (CNV). A recent report of nonrecurrent duplications associated with Pelizaeus-Merzbacher disease identified three distinctive characteristics. First, the majority of events can be seen to be complex, showing discontinuous duplications mixed with deletions, inverted duplications, and triplications. Second, junctions at endpoints show microhomology of 2–5 base pairs (bp). Third, endpoints occur near pre-existing low copy repeats (LCRs). Using these observations and evidence from DNA repair in other organisms, we derive a model of microhomology-mediated break-induced replication (MMBIR) for the origin of CNV and, ultimately, of LCRs. We propose that breakage of replication forks in stressed cells that are deficient in homologous recombination induces an aberrant repair process with features of break-induced replication (BIR). Under these circumstances, single-strand 3′ tails from broken replication forks will anneal with microhomology on any single-stranded DNA nearby, priming low-processivity polymerization with multiple template switches generating complex rearrangements, and eventual re-establishment of processive replication

Venous spread of renal cell carcinoma: MDCT

BACKGROUND: The purpose of our study was to present multidetector computed tomography (MDCT) findings in venous spread of renal cell carcinoma (RCC), to determine the superior extent of tumor thrombus and to compare MDCT findings with surgical report. ----- METHODS: The prospective MDCT study was performed on 31 patients diagnosed with RCC with venous spread (19 males and 12 females; age range 39-80 years; mean age 62.6 years). CT scans were obtained by MDCT scanner, in triphasic scanning protocol. All postprocessing techniques were performed by two independent radiologists, and the findings were reported in their consensus. MDCT diagnosis was compared with surgical and pathohistological findings. ----- RESULTS: Tumor thrombus extension into renal vein only (T3b stage) was found in 13/31 (42%) patients. Involvement of infradiaphragmatic level of inferior vena cava (IVC) (T3c stage) was found in 14/31 (45%) patients and supradiaphragmatic level of IVC (T4b stage) in 4/31 (13%) patients. In 27/31 (87%) patients surgery was performed, while 4/31 (13%) could not undergo surgery. In comparison with surgical report, in 25/27 (93%) operated patients the upper extent of the tumor thrombus was correctly diagnosed by MDCT, and 2/27 (7%) patients were falsely diagnosed. ----- CONCLUSION: MDCT represents a fast, relatively inexpensive, and reliable diagnostic method for evaluating the venous spread of RCC as well as the level of its upper extent. Triphasic MDCT is often the only diagnostic method necessary for planning the surgical procedure. Surgery should be performed as soon as possible for MDCT findings to be valid

Chromosomal phenotypes and submicroscopic abnormalities

<p>Abstract</p> <p>The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.</p