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11. A dual-mechanism antibiotic kills Gram-negative bacteria and avoids drug resistance

Author(s):
Martin, James K; Sheehan, Joseph P; Bratton, Benjamin P; Moore, Gabriel M; Mateus, André; Li, Sophia Hsin-Jung; Kim, Hahn; Rabinowitz, Joshua D; Typas, Athanasios; Savitski, Mikhail M; Wilson, Maxwell Z; Gitai, Zemer
Abstract:
The rise of antibiotic resistance and declining discovery of new antibiotics have created a global health crisis. Of particular concern, no new antibiotic classes have been approved for treating Gram-negative pathogens in decades. Here, we characterize a compound, SCH-79797, that kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism of action (MoA) with undetectably-low resistance frequencies. To characterize its MoA, we combined quantitative imaging, proteomic, genetic, metabolomic, and cell-based assays. This pipeline demonstrates that SCH-79797 has two independent cellular targets, folate metabolism and bacterial membrane integrity, and outperforms combination treatments in killing MRSA persisters. Building on the molecular core of SCH-79797, we developed a derivative, Irresistin-16, with increased potency and showed its efficacy against Neisseria gonorrheae in a mouse vaginal infection model. This promising antibiotic lead suggests that combining multiple MoAs onto a single chemical scaffold may be an underappreciated approach to targeting challenging bacterial pathogens.
Type:
Dataset
Issue Date:
20 May 2020

12. Data from a flume experiment of passive scalar diffusion within vegetation canopies using laser-induced fluorescence

Author(s):
Ghannam, Khaled; Poggi, Davide; Katul, Gabriel; Bou-Zeid, Elie
Abstract:
This dataset is a sequence of laser-induced fluorescence images of a dye injected in a channel flow with canopy-like stainless steel rods simulating a vegetation canopy stand. The data is acquired close to the channel bottom at z/h=0.2, where z is the height referenced to the channel bed and h is the canopy height. The dataset provides spatial distribution of scalar concentration in a plane parallel to the channel bed. The data has been used (but the data itself has not been published or available to the public) in previous work. The references are: Ghannam, K., Poggi, D., Porporato, A., & Katul, G. (2015). The spatio-temporal statistical structure and ergodic behaviour of scalar turbulence within a rod canopy. Boundary-Layer Meteorology,157(3), 447–460. Ghannam, K, Poggi, D., Bou-Zeid, E., Katul, G. (2020). Inverse cascade evidenced by information entropy of passive scalars in submerged canopy flows. Geophysical Research Letters (accepted).
Type:
Dataset
Issue Date:
22 April 2020

13. Distinct cytoskeletal proteins define zones of enhanced cell wall synthesis in Helicobacter pylori

Author(s):
Taylor, Jenny A.; Bratton, Benjamin P.; Sichel, Sophie R.; Blair, Kris M.; Jacobs, Holly M.; DeMeester, Kristen E.; Kuru, Erkin; Gray, Joe; Biboy, Jacob; VanNieuwenhze, Michael S.; Vollmer, Waldemar; Grimes, Catherine L.; Shaevitz, Joshua W.; Salama, Nina R.
Abstract:
Helical cell shape is necessary for efficient stomach colonization by Helicobacter pylori, but the molecular mechanisms for generating helical shape remain unclear. We show that the helical centerline pitch and radius of wild-type H. pylori cells dictate surface curvatures of considerably higher positive and negative Gaussian curvatures than those present in straight- or curved-rod bacteria. Quantitative 3D microscopy analysis of short pulses with either N-acetylmuramic acid or D-alanine metabolic probes showed that cell wall growth is enhanced at both sidewall curvature extremes. Immunofluorescence revealed MreB is most abundant at negative Gaussian curvature, while the bactofilin CcmA is most abundant at positive Gaussian curvature. Strains expressing CcmA variants with altered polymerization properties lose helical shape and associated positive Gaussian curvatures. We thus propose a model where CcmA and MreB promote PG synthesis at positive and negative Gaussian curvatures, respectively, and that this patterning is one mechanism necessary for maintaining helical shape.
Type:
Dataset and Image
Issue Date:
April 2019

14. Climate Impacts from Large Volcanic Eruptions in a High-resolution Climate Model: the Importance of Forcing Structure

Author(s):
Yang, Wenchang; Vecchi, Gabriel; Fueglistaler, Stephan; Horowitz, Larry; Luet, David; Muñoz, Ángel; Paynter, David; Underwood, Seth
Abstract:
Explosive volcanic eruptions have large climate impacts, and can serve as observable tests of the climatic response to radiative forcing. Using a high resolution climate model, we contrast the climate responses to Pinatubo, with symmetric forcing, and those to Santa Maria and Agung, which had meridionally asymmetric forcing. Although Pinatubo had larger global-mean forcing, asymmetric forcing strongly shifts the latitude of tropical rainfall features, leading to larger local precipitation/TC changes. For example, North Atlantic TC activity over is enhanced/reduced by SH-forcing (Agung)/NH-forcing (Santa Maria), but changes little in response to the Pinatubo forcing. Moreover, the transient climate sensitivity estimated from the response to Santa Maria is 20% larger than that from Pinatubo or Agung. This spread in climatic impacts of volcanoes needs to be considered when evaluating the role of volcanoes in global and regional climate, and serves to contextualize the well-observed response to Pinatubo.
Type:
Dataset
Issue Date:
2019

16. Fast animal pose estimation using deep neural networks

Author(s):
Pereira, Talmo D.; Aldarondo, Diego E.; Willmore, Lindsay; Kislin, Mikhail; Wang, Samuel S.-H.; Murthy, Mala; Shaevitz, Joshua W.
Abstract:
Recent work quantifying postural dynamics has attempted to define the repertoire of behaviors performed by an animal. However, a major drawback to these techniques has been their reliance on dimensionality reduction of images which destroys information about which parts of the body are used in each behavior. To address this issue, we introduce a deep learning-based method for pose estimation, LEAP (LEAP Estimates Animal Pose). LEAP automatically predicts the positions of animal body parts using a deep convolutional neural network with as little as 10 frames of labeled data for training. This framework consists of a graphical interface for interactive labeling of body parts and software for training the network and fast prediction on new data (1 hr to train, 185 Hz predictions). We validate LEAP using videos of freely behaving fruit flies (Drosophila melanogaster) and track 32 distinct points on the body to fully describe the pose of the head, body, wings, and legs with an error rate of <3% of the animal's body length. We recapitulate a number of reported findings on insect gait dynamics and show LEAP's applicability as the first step in unsupervised behavioral classification. Finally, we extend the method to more challenging imaging situations (pairs of flies moving on a mesh-like background) and movies from freely moving mice (Mus musculus) where we track the full conformation of the head, body, and limbs.
Type:
Dataset
Issue Date:
30 May 2018

17. Regional hydroclimatic variability due to contemporary deforestation in southern Amazonia and associated boundary layer characteristics

Author(s):
Khanna, Jaya; Medvigy, David; Fisch, Gilberto; Neves, Theomar Trindade de Araújo Tiburtino
Abstract:
Amazonian deforestation causes systematic changes in regional dry season precipitation. Some of these changes at contemporary large scales (a few hundreds of kilometers) of deforestation have been associated with a ‘dynamical mesoscale circulation’, induced by the replacement of rough forest with smooth pasture. In terms of decadal averages, this dynamical mechanism yields increased precipitation in downwind regions and decreased precipitation in upwind regions of deforested areas. Daily, seasonal, and interannual variations in this phenomenon may exist, but have not yet been identified or explained. This study uses observations and numerical simulations to develop relationships between the dynamical mechanism and the local- and continental-scale atmospheric conditions across a range of time scales. It is found that the strength of the dynamical mechanism is primarily controlled by the regional-scale thermal and dynamical conditions of the boundary layer, and not by the continental- and global-scale atmospheric state. Lifting condensation level and wind speed within the boundary layer have large and positive correlations with the strength of the dynamical mechanism. The strength of these relationships depends on time scale and is strongest over the seasonal cycle. Overall, the dynamical mechanism is found to be strongest during times when the atmosphere is relatively stable. Hence, for contemporary large scales of deforestation this phenomenon is found to be the prevalent convective triggering mechanism during the dry and parts of transition seasons (especially during the dry-to-wet transition), significantly affecting the hydroclimate during this period.
Type:
Dataset and Software
Issue Date:
2018

18. Data for Nature Climate Change article 'Regional dry-season climate changes due to three decades of Amazonian deforestation'

Author(s):
Khanna, Jaya; Medvigy, David; Fueglistaler, Stephan; Walko, Robert
Abstract:
More than 20% Amazon rainforest has been cleared in the past three decades triggering important hydroclimatic changes. Small-scale (~few kilometers) deforestation in the 1980s has caused thermally-triggered atmospheric circulations that increase regional cloudiness and precipitation frequency. However, these circulations are predicted to diminish as deforestation increases. Here we use multi-decadal satellite records and numerical model simulations to show a regime shift in the regional hydroclimate accompanying increasing deforestation in Rondônia, Brazil. Compared to the 1980s, present-day deforested areas in downwind western Rondônia are found to be wetter than upwind eastern deforested areas during the local dry season. The resultant precipitation change in the two regions is approximately ±25% of the deforested area mean. Meso-resolution simulations robustly reproduce this transition when forced with increasing deforestation alone, showing a negligible role of large-scale climate variability. Furthermore, deforestation-induced surface roughness reduction is found to play an essential role in the present-day dry season hydroclimate. Our study illustrates the strong scale-sensitivity of the climatic response to Amazonian deforestation and suggests that deforestation is sufficiently advanced to have caused a shift from a thermally- to a dynamically-driven hydroclimatic regime.
Type:
Dataset and Software
Issue Date:
2017

20. Sherlock Movie Watching Dataset

Author(s):
Chen, Janice
Abstract:
Our daily lives revolve around sharing experiences and memories with others. When different people recount the same events, how similar are their underlying neural representations? In this study, participants viewed a fifty-minute audio-visual movie, then verbally described the events while undergoing functional MRI. These descriptions were completely unguided and highly detailed, lasting for up to forty minutes. As each person spoke, event-specific spatial patterns were reinstated (movie-vs.-recall correlation) in default network, medial temporal, and high-level visual areas; moreover, individual event patterns were highly discriminable and similar between people during recollection (recall-vs.-recall similarity), suggesting the existence of spatially organized memory representations. In posterior medial cortex, medial prefrontal cortex, and angular gyrus, activity patterns during recall were more similar between people than to patterns elicited by the movie, indicating systematic reshaping of percept into memory across individuals. These results reveal striking similarity in how neural activity underlying real-life memories is organized and transformed in the brains of different people as they speak spontaneously about past events.
Type:
Dataset
Issue Date:
26 October 2016

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