Analysis of Microtubule Sliding Patterns in Chlamydomonas Flagellar Axonemes Reveals Dynein Activity on Specific Doublet Microtubules

Generating the complex waveforms characteristic of beating eukaryotic cilia and flagella requires spatial regulation of dynein-driven microtubule sliding. To generate bending, one prediction is that dynein arms alternate between active and inactive forms on specific subsets of doublet microtubules. Using an in vitro microtubule sliding assay combined with a structural approach, we determined that ATP induces sliding between specific subsets of doublet microtubules, apparently capturing one phase of the beat cycle. These studies were also conducted using high Ca2+ conditions. InChlamydomonas, high Ca2+ induces changes in waveform which are predicted to result from regulating dynein activity on specific microtubules. Our results demonstrate that microtubule sliding in high Ca2+ buffer is also induced by dynein arms on specific doublets. However, the pattern of microtubule sliding in high Ca2+ buffer significantly differs from that in low Ca2+. These results are consistent with a ‘switching hypothesis’ of axonemal bending and provide evidence to indicate that Ca2+ control of waveform includes modulation of the pattern of microtubule sliding between specific doublets. In addition, analysis of microtubule sliding in mutant axonemes reveals that the control mechanism is disrupted in some mutants

School support, chaos, routines, and parents' mental health during COVID-19 remote schooling

Remote schooling due to Coronavirus Disease 2019 (COVID-19) created profound challenges for families. In this investigation, we examined parents' depression and anxiety during remote schooling and their associations with parents' reports of school support. We also evaluated indirect and interactive (i.e., moderation) associations. Participants were parents (N = 152, 92.8% mothers, 65.1% Black) from an urban area with high rates of COVID-19. Of the 152 parents, 27.6% reported elevated levels of depression and 34.2% reported elevated anxiety. Regression analyses showed that school support was negatively associated with parents' depression (β = -.33, p < .01) and anxiety (β = -.21, p < .01). There was an indirect association between school support and parents' mental health via household chaos and daily routines. Reported COVID-19 impact moderated the direct association between school support and parental depression and anxiety. There was a statistically significant association between school support and parents' depression and anxiety when COVID-19 impact was low or moderate, but not when COVID-19 impact was high. These results may suggest that for parents who were not highly impacted by the pandemic, school support buffered the association between stress and parents' mental health problems; parents most impacted by COVID-19 may need additional support. (PsycInfo Database Record (c) 2022 APA, all rights reserved).K01 MH110600 - NIMH NIH HHS; L40 MH117714 - NIMH NIH HHSAccepted manuscrip

Network Analysis of Gut Microbiome Throughout a Whole Foods Based High Fiber Dietary Intervention Reveals Complex Community Dynamics in Melanoma Survivors

https://openworks.mdanderson.org/sumexp22/1139/thumbnail.jp

Tuning the Magnetic Transport of an Induction LINAC using Emittance

The Lawrence Livermore National Laboratory Flash X-Ray (FXR) machine is a linear induction accelerator used to produce a nominal 18 MeV, 3 kA, 65 ns pulse width electron beam for hydrodynamic radiographs. A common figure of merit for this type of radiographic machine is the x-ray dose divided by the spot area on the bremsstrahlung converter where a higher FOM is desired. Several characteristics of the beam affect the minimum attainable x-ray spot size. The most significant are emittance (chaotic transverse energy), chromatic aberration (energy variation), and beam motion (transverse instabilities and corkscrew motion). FXR is in the midst of a multi-year optimization project to reduce the spot size. This paper describes the effort to reduce beam emittance by adjusting the fields of the transport solenoids and position of the cathode. If the magnetic transport is not correct, the beam will be mismatched and undergo envelope oscillations increasing the emittance. We measure the divergence and radius of the beam in a drift section after the accelerator by imaging the optical transition radiation (OTR) and beam envelope on a foil. These measurements are used to determine an emittance. Relative changes in the emittance can be quickly estimated from the foil measurements allowing for an efficient, real-time study. Once an optimized transport field is determined, the final focus can be adjusted and the new x-ray spot measured. A description of the diagnostics and analysis is presented

Impact of a Whole Foods Based High Fiber Diet on Gut Microbiome in Melanoma Survivors

https://openworks.mdanderson.org/sumexp21/1237/thumbnail.jp

The 50 Constellation Priority Sites

The Constellation program (CxP) has developed a list of 50 sites of interest on the Moon which will be targeted by the LRO narrow angle camera. The list has also been provided to the M~ team to supplement their targeting list. This list does not represent a "site selection" process; rather the goal was to find "representative" sites and terrains to understand the range of possible surface conditions for human lunar exploration to aid engineering design and operational planning. The list compilers leveraged heavily on past site selection work (e.g. Geoscience and a Lunar Base Workshop - 1988, Site Selection Strategy for a Lunar Outpost - 1990, Exploration Systems Architecture Study (ESAS) - 2005). Considerations included scientific, resource utilization, and operational merits, and a desire to span lunar terrain types. The targets have been organized into two "tiers" of 25 sites each to provide a relative priority ranking in the event of mutual interference. A LEAG SAT (special action team) was established to validate and recommend modifications to the list. This SAT was chaired by Dr. Paul Lucey. They provided their final results to CxP in May. Dr. Wendell Mendell will organize an on-going analysis of the data as they come down to ensure data quality and determine if and when a site has sufficient data to be retired from the list. The list was compiled using the best available data, however, it is understood that with the flood of new lunar data, minor modifications or adjustments may be required

Anthocyanin management in fruits by fertilization

Anthocyanins are water-soluble vacuolar plant pigments that are mainly synthesized in epidermal layers and the flesh of fruits such as apples, cherries, grapes, and other berries. Because of their attractive red to purple coloration and their health-promoting potential, anthocyanins are significant determinants for the quality and market value of fruits and fruit-derived products. In crops, anthocyanin accumulation in leaves can be caused by nutrient deficiency which is usually ascribed to insufficient nitrogen or phosphorus fertilization. However, it is a little-known fact that the plant’s nutrient status also impacts anthocyanin synthesis in fruits. Hence, strategic nutrient supply can be a powerful tool to modify the anthocyanin content and consequently the quality and market value of important agricultural commodities. Here we summarize the current knowledge of the influence of plant nutrients on anthocyanin synthesis in fruits of major global market value and discuss the underlying cellular processes that integrate nutrient signaling with fruit anthocyanin formation. It is highlighted that fertilization that is finely tuned in amount and timing has the potential to positively influence the fruit quality by regulating anthocyanin levels. We outline new approaches to enrich plant based foods with health-promoting anthocyanins

Systematic identification of signaling pathways with potential to confer anticancer drug resistance

Cancer cells can activate diverse signaling pathways to evade the cytotoxic action of drugs. We created and screened a library of barcoded pathway-activating mutant complementary DNAs to identify those that enhanced the survival of cancer cells in the presence of 13 clinically relevant, targeted therapies. We found that activation of the RAS-MAPK (mitogen-activated protein kinase), Notch1, PI3K (phosphoinositide 3-kinase)–mTOR (mechanistic target of rapamycin), and ER (estrogen receptor) signaling pathways often conferred resistance to this selection of drugs. Activation of the Notch1 pathway promoted acquired resistance to tamoxifen (an ER-targeted therapy) in serially passaged breast cancer xenografts in mice, and treating mice with a γ-secretase inhibitor to inhibit Notch signaling restored tamoxifen sensitivity. Markers of Notch1 activity in tumor tissue correlated with resistance to tamoxifen in breast cancer patients. Similarly, activation of Notch1 signaling promoted acquired resistance to MAPK inhibitors in BRAF[superscript V600E] melanoma cells in culture, and the abundance of Notch1 pathway markers was increased in tumors from a subset of melanoma patients. Thus, Notch1 signaling may be a therapeutic target in some drug-resistant breast cancers and melanomas. Additionally, multiple resistance pathways were activated in melanoma cell lines with intrinsic resistance to MAPK inhibitors, and simultaneous inhibition of these pathways synergistically induced drug sensitivity. These data illustrate the potential for systematic identification of the signaling pathways controlling drug resistance that could inform clinical strategies and drug development for multiple types of cancer. This approach may also be used to advance clinical options in other disease contexts.National Institutes of Health (U.S.) (Grant CA103866)National Institutes of Health (U.S.) (Grant AI07389

Absence of Membrane Phosphatidylcholine Does Not Affect Virulence and Stress Tolerance Phenotypes in the Opportunistic Pathogen Pseudomonas aeruginosa

During growth in presence of choline, both laboratory and clinical Pseudomonas aeruginosa strains synthesize phosphatidylcholine (PC), and PC makes up ∼4% of the total membrane phospholipid content. In all the strains tested, PC synthesis occurred only when choline is provided exogenously. Mutants defective in synthesis of PC were generated in the strain backgrounds PAO1 and PA14. Minimum inhibitory concentration studies testing sensitivity of PC-deficient strains towards various antibiotics and cationic antimicrobial peptides revealed no differences as compared to wild-type strains. Mutants incapable of synthesizing PC were also found to be unaffected in motility and biofilm formation on abiotic surfaces, colonization of biotic surfaces and virulence in a mouse infection model. A global phenotypic microarray was further used to identify conditions wherein membrane PC may play a role of in P. aeruginosa. No culture conditions were identified wherein wild-type and PC-deficient mutants showed phenotypic differences. Membrane PC may serve a highly specific role during P. aeruginosa interactions with its eukaryotic hosts based on all the clinical strains tested retaining the ability to synthesize it during availability of choline