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Simple Summary: Building on the idea of a germline oligogenic origin of lung cancer, we performed WES of DNA from patients' peripheral blood and their unaffected sibs. Filtering for rare variants and potentially damaging effects, we identified 40 deleterious variants mapping in genes previously associated with cancer exclusively identified in patients. Transcriptome profiling on both tumor and normal lung tissues revealed that, among the selected mutated genes, 16 variants mapping in 16 genes were either down- or upregulated in cancer specimens. Among the downregulated genes, 9 variants in 9 genes carried the mutated allele suggesting a loss of heterozygosity. Notably, the group of mutated genes was unique for each patient, pinpointing to a "private" oligogenic germline signature. In the era of precision medicine, this report emphasizes the importance of an "omic" approach to uncover an oligogenic germline signature underlying cancer development and identify suitable therapeutic targets. Lung cancer (LC) continues to be an important public health problem, being the most common form of cancer and a major cause of cancer deaths worldwide. Despite the great bulk of research to identify genetic susceptibility genes by genome-wide association studies, only few loci associated to nicotine dependence have been consistently replicated. Our previously published study in few phenotypically discordant sib-pairs identified a combination of germline truncating mutations in known cancer susceptibility genes in never-smoker early-onset LC patients, which does not present in their healthy sib. These results firstly demonstrated the presence of an oligogenic combination of disrupted cancer-predisposing genes in non-smokers patients, giving experimental support to a model of a "private genetic epidemiology". Here, we used a combination of whole-exome and RNA sequencing coupled with a discordant sib's model in a novel cohort of pairs of never-smokers early-onset LC patients and in their healthy sibs used as controls. We selected rare germline variants predicted as deleterious by CADD and SVM bioinformatics tools and absent in the healthy sib. Overall, we identified an average of 200 variants per patient, about 10 of which in cancer-predisposing genes. In most of them, RNA sequencing data reinforced the pathogenic role of the identified variants showing: (i) downregulation in LC tissue (indicating a "second hit" in tumor suppressor genes); (ii) upregulation in cancer tissue (likely oncogene); and (iii) downregulation in both normal and cancer tissue (indicating transcript instability). The combination of the two techniques demonstrates that each patient has an average of six (with a range from four to eight) private mutations with a functional effect in tumor-predisposing genes. The presence of a unique combination of disrupting events in the affected subjects may explain the absence of the familial clustering of non-small-cell lung cancer. In conclusion, these findings indicate that each patient has his/her own "predisposing signature" to cancer development and suggest the use of personalized therapeutic strategies in lung cancer. [ABSTRACT FROM AUTHOR]

New experimental techniques are allowing, for the first time, direct visualization of mass and momentum transport across the sediment-water interface in streams. These experimental insights are catalyzing a renaissance in our understanding of the role stream turbulence plays in a host of critical ecosystem services, including nutrient cycling. In this commentary, we briefly review the nature of stream turbulence and its role in hyporheic exchange and nutrient cycling in streams. A simple process-based model, borrowed from biochemical engineering, provides the link between empirical relationships for grain-scale turbulent mixing and nutrient processing at reach, catchment, continental, and global scales.

Water flow on plant canopies determines the partitioning of intercepted rainfall between stemflow and throughflow, yet understanding of these flow processes remains minimally developed. Plant canopies may concentrate intercepted water into rivulets that flow beneath branches. If the rivulets remain attached to branches until they encounter the main tree trunk, they form stemflow. If the rivulets detach from branches, however, they form 'pour points', regions of concentrated throughfall. Here, rivulet flow below uniform cylinders was studied experimentally. Experimental observations were interpreted using hydrodynamic theory to predict the likelihood of a rivulet detaching based on a critical rivulet height (λc$$ {\lambda}_c $$). Predictions of rivulet detachment were explored for a simplified case where water is introduced at known flow rates at a discrete point above a uniform, cylindrical 'branch'. Where the branch was straight, the percentage of trials forming a rivulet, or the rivulet formation rate, increased with increasing branch inclination angle to the horizontal axis. Rivulet formation rates did not vary with flow rate. However, the volume of water collected at the end of the branch, analogous to stemflow, decreased with a higher flow rates due to the formation of flow instabilities. Rivulets forming on straight branches did not detach. Instead, the rivulet stream accelerated and reduced in height as it flowed along the cylinder. Rivulets formed on curved branches detached only when the branch axis after the curve approached the horizontal. Future theoretical and experimental studies can extend this work to improve understanding of more complex surfaces and branch architectures to mechanistically understand canopy interception. [ABSTRACT FROM AUTHOR]

Although there is a range of approaches for classifying the wake structure behind an array of obstacles, these approaches provide inconsistent results across different array systems. This motivates the present study to integrate and reconcile these approaches into one that is consistent across different systems. This new, transferable classification approach is based on the dimensionless flow blockage of the array and the wake stability parameter. To demonstrate this approach, a series of laboratory experiments was conducted to characterise the wake structure behind an array of emergent cylinders across a practically relevant parameter space that has not previously been explored. Two arrays with the same values of flow blockage and wake stability parameters but different sizes display the same wake structure, demonstrating the controlling influence of these two parameters on the wake structure. This approach classifies four different wake structures, which are distinct in that they display differences in instantaneous and time-averaged flow fields, temporal velocity oscillations, shear layer growth and the length of the steady wake region. The dependence of the wake structure on the two parameters is a consequence of (i) the controlling influence of blockage on the fraction of incident flow passing through the array and (ii) the ability of shallowness to suppress wake instabilities and, to a lesser extent, also influence the velocity through the array. This paper provides a predictive framework for the wake structure based on knowledge of the array geometry, and the depth and velocity of incident flow across the entire relevant practical parameter space. [ABSTRACT FROM AUTHOR]

Video abstractAt Mistaken Point, Newfoundland, Canada, rangeomorph "fronds" dominate the earliest (579-565 million years ago) fossil communities of large (0.1 to 2 m height) multicellular benthic eukaryotes. They lived in low-flow environments, fueled by uptake [1-3] of dissolved reactants (osmotrophy). However, prokaryotes are effective osmotrophs, and the advantage of taller eukaryotic osmotrophs in this deep-water community context has not been addressed. We reconstructed flow-velocity profiles and vertical mixing using canopy flow models appropriate to the densities of the observed communities. Further modeling of processes at organismal surfaces documents increasing uptake with height in the community as a function of thinning of the diffusive boundary layer with increased velocity. The velocity profile, produced by canopy flow in the community, generates this advantage of upward growth. Alternative models of upward growth advantage based on redox/resource gradients fail, given the efficiency of vertical mixing. In benthic communities of osmotrophs of sufficient density, access to flow in low-flow settings provides an advantage to taller architecture, providing a selectional driver for communities of tall eukaryotes in contexts where phototropism cannot contribute to upward growth. These Ediacaran deep-sea fossils were preserved during the increasing oxygenation prior to the Cambrian radiation of animals and likely represent an important phase in the ecological and evolutionary transition to more complex eukaryotic forms.