Backup without redundancy: genetic interactions reveal the cost of duplicate gene loss.

Many genes can be deleted with little phenotypic consequences. By what mechanism and to what extent the presence of duplicate genes in the genome contributes to this robustness against deletions has been the subject of considerable interest. Here, we exploit the availability of high-density genetic interaction maps to provide direct support for the role of backup compensation, where functionally overlapping duplicates cover for the loss of their paralog. However, we find that the overall contribution of duplicates to robustness against null mutations is low ( approximately 25%). The ability to directly identify buffering paralogs allowed us to further study their properties, and how they differ from non-buffering duplicates. Using environmental sensitivity profiles as well as quantitative genetic interaction spectra as high-resolution phenotypes, we establish that even duplicate pairs with compensation capacity exhibit rich and typically non-overlapping deletion phenotypes, and are thus unable to comprehensively cover against loss of their paralog. Our findings reconcile the fact that duplicates can compensate for each other's loss under a limited number of conditions with the evolutionary instability of genes whose loss is not associated with a phenotypic penalty

"Rho"ing a Cellular Boat with Rearward Membrane Flow.

The physicist Edward Purcell wrote in 1977 about mechanisms that cells could use to propel themselves in a low Reynolds number environment. Reporting in Developmental Cell, O'Neill et al. (2018) provide direct evidence for one of these mechanisms by optogenetically driving the migration of cells suspended in liquid through RhoA activation

A strategy for extracting and analyzing large-scale quantitative epistatic interaction data

Recently, approaches have been developed for high-throughput identification of synthetic sick/lethal gene pairs. However, these are only a specific example of the broader phenomenon of epistasis, wherein the presence of one mutation modulates the phenotype of another. We present analysis techniques for generating high-confidence quantitative epistasis scores from measurements made using synthetic genetic array and epistatic miniarray profile (E-MAP) technology, as well as several tools for higher-level analysis of the resulting data that are greatly enhanced by the quantitative score and detection of alleviating interactions

Defining the current distribution of the imperiled Black-spotted Newt across south Texas, USA

The Black-spotted Newt (Notophthalmus meridionalis) is a chronically understudied salamander species, with many aspects of its natural history, ecology, and distribution poorly known. Previous studies using traditional methodologies have had limited success documenting N. meridionalis on the landscape, detecting individuals at 6% (7 of 114) and 1% (2 of 221) of sites surveyed. A novel environmental DNA (eDNA) assay was designed and implemented with the goals of assessing the current distribution of N. meridionalis across south Texas, USA, and better understanding the conditions for positive eDNA detections. We conducted eDNA sampling and traditional surveys at 80 sites throughout south Texas. Notophthalmus meridionalis was detected at 12 localities in total: four localities using eDNA surveys, four localities using traditional methods, and four localities with both methodologies. eDNA detections were obtained from five counties, including one where N. meridionalis has never been reported and another where N. meridionalis has not been observed since the 1930s. eDNA detections were obtained in all four seasons, generally following moderate to heavy rainfall events. Our results support the increased use of eDNA surveys to detect rare and cryptic amphibians and to better understand the current distribution of this imperiled species

Mechanism of Prion Propagation: Amyloid Growth Occurs by Monomer Addition

Abundant nonfibrillar oligomeric intermediates are a common feature of amyloid formation, and these oligomers, rather than the final fibers, have been suggested to be the toxic species in some amyloid diseases. Whether such oligomers are critical intermediates for fiber assembly or form in an alternate, potentially separable pathway, however, remains unclear. Here we study the polymerization of the amyloidogenic yeast prion protein Sup35. Rapid polymerization occurs in the absence of observable intermediates, and both targeted kinetic and direct single-molecule fluorescence measurements indicate that fibers grow by monomer addition. A three-step model (nucleation, monomer addition, and fiber fragmentation) accurately accounts for the distinctive kinetic features of amyloid formation, including weak concentration dependence, acceleration by agitation, and sigmoidal shape of the polymerization time course. Thus, amyloid growth can occur by monomer addition in a reaction distinct from and competitive with formation of potentially toxic oligomeric intermediates

A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria

Health-Related Quality of Life After Stereotactic Body Radiation Therapy for Localized Prostate Cancer: Results From a Multi-institutional Consortium of Prospective Trials

PurposeTo evaluate the early and late health-related quality of life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT).Methods and MaterialsPatient self-reported QOL was prospectively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer. Data from the Expanded Prostate Cancer Index Composite (EPIC) instrument were obtained at baseline and at regular intervals up to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short course of androgen deprivation therapy was given to 14% of patients.ResultsMedian follow-up was 3 years and 194 patients remained evaluable at 5 years. A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities. Sexual QOL decline was predominantly observed within the first 9 months, a pattern not altered by the use of androgen deprivation therapy or patient age.ConclusionLong-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL. A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels. With a large number of patients evaluable up to 5 years following SBRT, it is unlikely that unexpected late adverse effects will manifest themselves

Decoration of plasmonic Mg nanoparticles by partial galvanic replacement.

Plasmonic structures have attracted much interest in science and engineering disciplines, exploring a myriad of potential applications owing to their strong light-matter interactions. Recently, the plasmonic concentration of energy in subwavelength volumes has been used to initiate chemical reactions, for instance by combining plasmonic materials with catalytic metals. In this work, we demonstrate that plasmonic nanoparticles of earth-abundant Mg can undergo galvanic replacement in a nonaqueous solvent to produce decorated structures. This method yields bimetallic architectures where partially oxidized 200-300 nm Mg nanoplates and nanorods support many smaller Au, Ag, Pd, or Fe nanoparticles, with potential for a stepwise process introducing multiple decoration compositions on a single Mg particle. We investigated this mechanism by electron-beam imaging and local composition mapping with energy-dispersive X-ray spectroscopy as well as, at the ensemble level, by inductively coupled plasma mass spectrometry. High-resolution scanning transmission electron microscopy further supported the bimetallic nature of the particles and provided details of the interface geometry, which includes a Mg oxide separation layer between Mg and the other metal. Depending on the composition of the metallic decorations, strong plasmonic optical signals characteristic of plasmon resonances were observed in the bulk with ultraviolet-visible spectrometry and at the single particle level with darkfield scattering. These novel bimetallic and multimetallic designs open up an exciting array of applications where one or multiple plasmonic structures could interact in the near-field of earth-abundant Mg and couple with catalytic nanoparticles for applications in sensing and plasmon-assisted catalysis.Support for this project was provided by the EU Framework Programme for Research and Innovation Horizon 2020 (Starting Grant SPECs 804523). J.A. wishes to acknowledge financial support from Natural Sciences and Engineering Research Council of Canada and “Fonds de Recherche Québec – Nature et Technologies” postdoctoral fellowships (BP and B3X programs). C.B. is thankful for funding from the Engineering and Physical Sciences Research Council (Standard Research Studentship (DTP) EP/R513180/1), and E.R.H. for support from the EPSRC NanoDTC Cambridge (EP/L015978/1). S.M.C. acknowledges support from the Henslow Research Fellowship at Girton College, Cambridge. We acknowledge access and support in the use of the electron Physical Sciences Imaging Centre (MG21980) at the Diamond Light Source, U.K

The Effect Of Mild Exercise Induced Dehydration On Sport Concussion Assessment Tool 3 (SCAT3) Scores: A within-subjects design.

# Background Sports-related concussions are prevalent in the United States. Various diagnostic tools are utilized in order to monitor deviations from baseline in memory, reaction time, symptoms, and balance. Evidence indicates that dehydration may also alter the results of diagnostic tests. # Purpose The purpose was to determine the effect of exercise-induced dehydration on performance related to concussion examination tools. # Study Design Repeated measures design. # Methods Seventeen recreationally competitive, non-concussed participants (age: 23.1±3.1 years, height:168.93±10.71 cm, mass: 66.16 ± 6.91 kg) performed three thermoneutral, counterbalanced sessions (rested control, euhydrated, dehydrated). Participants were either restricted (0.0 L/hr) or provided fluids (1.0 L/hr) while treadmill running for 60 min at an intensity equal to 65-70% age-predicted maximum heart rate (APMHR). The Sport Concussion Assessment Tool 3 (SCAT3) was utilized to assess symptoms, memory, balance, and coordination. # Results Statistically significant differences were seen among sessions for symptom severity and symptom total. The rested control session had significantly lower values when compared to the dehydrated session. Additionally, the symptom total in the rested control was significantly lower than the euhydrated condition as well. No statistically significant differences were seen for the BESS or memory scores. # Conclusions Mild exercise-induced dehydration results in increased self-reported symptoms associated with concussions. Clinicians tasked with monitoring and accurately diagnosing head trauma should take factors such as hydration status into account when assessing patients for concussion with the SCAT3. Clinicians should proceed with caution and not assume concussion as primary cause for symptom change. # Level of evidence Level