Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling

Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women

The American Association for the Surgery of Trauma renal injury grading scale: Implications of the 2018 revisions for injury reclassification and predicting bleeding interventions.

BackgroundIn 2018, the American Association for the Surgery of Trauma (AAST) published revisions to the renal injury grading system to reflect the increased reliance on computed tomography scans and non-operative management of high-grade renal trauma (HGRT). We aimed to evaluate how these revisions will change the grading of HGRT and if it outperforms the original 1989 grading in predicting bleeding control interventions.MethodsData on HGRT were collected from 14 Level-1 trauma centers from 2014 to 2017. Patients with initial computed tomography scans were included. Two radiologists reviewed the scans to regrade the injuries according to the 1989 and 2018 AAST grading systems. Descriptive statistics were used to assess grade reclassifications. Mixed-effect multivariable logistic regression was used to measure the predictive ability of each grading system. The areas under the curves were compared.ResultsOf the 322 injuries included, 27.0% were upgraded, 3.4% were downgraded, and 69.5% remained unchanged. Of the injuries graded as III or lower using the 1989 AAST, 33.5% were upgraded to grade IV using the 2018 AAST. Of the grade V injuries, 58.8% were downgraded using the 2018 AAST. There was no statistically significant difference in the overall areas under the curves between the 2018 and 1989 AAST grading system for predicting bleeding interventions (0.72 vs. 0.68, p = 0.34).ConclusionAbout one third of the injuries previously classified as grade III will be upgraded to grade IV using the 2018 AAST, which adds to the heterogeneity of grade IV injuries. Although the 2018 AAST grading provides more anatomic details on injury patterns and includes important radiologic findings, it did not outperform the 1989 AAST grading in predicting bleeding interventions.Level of evidencePrognostic and Epidemiological Study, level III

Possible Seasonality of Clostridium difficile in Retail Meat, Canada

We previously reported Clostridium difficile in 20% of retail meat in Canada, which raised concerns about potential foodborne transmissibility. Here, we studied the genetic diversity of C. difficile in retail meats, using a broad Canadian sampling infrastructure and 3 culture methods. We found 6.1% prevalence and indications of possible seasonality (highest prevalence in winter)

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Science and Curation Considerations for the Design of a Mars Sample Return (MSR) Sample Receiving Facility

The most important single element of the “ground system” portion of a Mars Sample Return (MSR) Campaign is a facility referred to as the Sample Receiving Facility (SRF), which would need to be designed and equipped to receive the returned spacecraft, extract and open the sealed sample container, extract the samples from the sample tubes, and implement a set of evaluations and analyses of the samples. One of the main findings of the first MSR Sample Planning Group (MSPG, 2019a) states that “The scientific community, for reasons of scientific quality, cost, and timeliness, strongly prefers that as many sample-related investigations as possible be performed in PI-led laboratories outside containment.” There are many scientific and technical reasons for this preference, including the ability to utilize advanced and customized instrumentation that may be difficult to reproduce inside in a biocontained facility, and the ability to allow multiple science investigators in different labs to perform similar or complementary analyses to confirm the reproducibility and accuracy of results. It is also reasonable to assume that there will be a desire for the SRF to be as efficient and economical as possible, while still enabling the objectives of MSR to be achieved. For these reasons, MSPG concluded, and MSPG2 agrees, that the SRF should be designed to accommodate only those analytical activities that could not reasonably be done in outside laboratories because they are time- or sterilization-sensitive, are necessary for the Sample Safety Assessment Protocol (SSAP), or are necessary parts of the initial sample characterization process that would allow subsamples to be effectively allocated for investigation. All of this must be accommodated in an SRF, while preserving the scientific value of the samples through maintenance of strict environmental and contamination control standards

Preliminary Planning for Mars Sample Return (MSR) Curation Activities in a Sample Receiving Facility

The Mars Sample Return Planning Group 2 (MSPG2) was tasked with identifying the steps that encompass all the curation activities that would happen within the MSR Sample Receiving Facility (SRF) and any anticipated curation-related requirements. An area of specific interest is the necessary analytical instrumentation. The SRF would be a Biosafety Level-4 facility where the returned MSR flight hardware would be opened, the sample tubes accessed, and the martian sample material extracted from the tubes. Characterization of the essential attributes of each sample would be required to provide enough information to prepare a sample catalog used in guiding the preparation of sample-related proposals by the world’s research community and informing decisions by the sample allocation committee. The sample catalog would be populated with data and information generated during all phases of activity, including data derived concurrent with Mars 2020 sample-collecting rover activity, sample transport to Earth, and initial sample characterization within the SRF. We conclude that initial sample characterization can best be planned as a set of three sequential phases, which we have called Pre-Basic Characterization (Pre-BC), Basic Characterization (BC), and Preliminary Examination (PE), each of which requires a certain amount of instrumentation. Data on specific samples and subsamples obtained during sample safety assessments and time-sensitive scientific investigations would also be added to the catalog. There are several areas where future work would be beneficial to prepare for the receipt of samples, which would include the design of a sample tube isolation chamber and a strategy for opening the sample tubes and removing dust from the tube exteriors

Planning Implications Related to Sterilization-Sensitive Science Investigations Associated with Mars Sample Return (MSR)

The NASA/ESA Mars Sample Return (MSR) Campaign seeks to establish whether life on Mars existed where and when environmental conditions allowed. Laboratory measurements on the returned samples are useful if what is measured is evidence of phenomena on Mars rather than of the effects of sterilization conditions. This report establishes that there are categories of measurements that can be fruitful despite sample sterilization and other categories that cannot. Sterilization kills living microorganisms and inactivates complex biological structures by breaking chemical bonds. Sterilization has similar effects on chemical bonds in non-biological compounds, including abiotic or pre-biotic reduced carbon compounds, hydrous minerals, and hydrous amorphous solids. We considered the sterilization effects of applying dry heat under two specific temperature-time regimes and the effects of γ-irradiation. Many measurements of volatile-rich materials are sterilization sensitive—they will be compromised by either dehydration or radiolysis upon sterilization. Dry-heat sterilization and γ-irradiation differ somewhat in their effects but affect the same chemical elements. Sterilization-sensitive measurements include the abundances and oxidation-reduction (redox) states of redox-sensitive elements, and isotope abundances and ratios of most of them. All organic molecules, and most minerals and naturally occurring amorphous materials that formed under habitable conditions, contain at least one redox-sensitive element. Thus, sterilization-sensitive evidence about ancient life on Mars and its relationship to its ancient environment will be severely compromised if the samples collected by Mars 2020 rover Perseverance cannot be analyzed in an unsterilized condition. To ensure that sterilization-sensitive measurements can be made even on samples deemed unsafe for unsterilized release from containment, contingency instruments in addition to those required for curation, time-sensitive science, and the Sample Safety Assessment Protocol would need to be added to the Sample Receiving Facility (SRF). Targeted investigations using analogs of MSR Campaign-relevant returned-sample types should be undertaken to fill knowledge gaps about sterilization effects on important scientific measurements, especially if the sterilization regimens eventually chosen are different from those considered in this report

The Scientific Importance of Returning Airfall Dust as a Part of Mars Sample Return (MSR)

Dust transported in the martian atmosphere is of intrinsic scientific interest and has relevance for the planning of human missions in the future. The MSR Campaign, as currently designed, presents an important opportunity to return serendipitous, airfall dust. The tubes containing samples collected by the Perseverance rover would be placed in cache depots on the martian surface perhaps as early as 2023–24 for recovery by a subsequent mission no earlier than 2028–29, and possibly as late as 2030–31. Thus, the sample tube surfaces could passively collect dust for multiple years. This dust is deemed to be exceptionally valuable as it would inform our knowledge and understanding of Mars’ global mineralogy, surface processes, surface-atmosphere interactions, and atmospheric circulation. Preliminary calculations suggest that the total mass of such dust on a full set of tubes could be as much as 100 mg and, therefore, sufficient for many types of laboratory analyses. Two planning steps would optimize our ability to take advantage of this opportunity: (1) the dust-covered sample tubes should be loaded into the Orbiting Sample container (OS) with minimal cleaning and (2) the capability to recover this dust early in the workflow within an MSR Sample Receiving Facility (SRF) would need to be established. A further opportunity to advance dust/atmospheric science using MSR, depending upon the design of the MSR Campaign elements, may lie with direct sampling and the return of airborne dust

Final Report of the MSR Science Planning Group 2 (MSPG2)

The Mars Sample Return (MSR) Campaign must meet a series of scientific and technical achievements to be successful. While the respective engineering responsibilities to retrieve the samples have been formalized through a Memorandum of Understanding between ESA and NASA, the roles and responsibilities of the scientific elements have yet to be fully defined. In April 2020, ESA and NASA jointly chartered the MSR Science Planning Group 2 (MSPG2) to build upon previous planning efforts in defining 1) an end-to-end MSR Science Program and 2) needed functionalities and design requirements for an MSR Sample Receiving Facility (SRF). The challenges for the first samples brought from another planet include not only maintaining and providing samples in pristine condition for study, but also maintaining biological containment until the samples meet sample safety criteria for distribution outside of biocontainment. The MSPG2 produced six reports outlining 66 findings. Abbreviated versions of the five additional high-level MSPG2 summary findings are: Summary-1. A long-term NASA/ESA MSR Science Program, along with the necessary funding and human resources, will be required to accomplish the end-to-end scientific objectives of MSR. Summary-2. MSR curation will need to be done concurrently with Biosafety Level-4 containment. This would lead to complex first-of-a-kind curation implementations and require further technology development. Summary-3. Most aspects of MSR sample science can, and should, be performed on samples deemed safe in laboratories outside of the SRF. However, other aspects of MSR sample science are both time-sensitive and sterilization-sensitive and would need to be carried out in the SRF. Summary-4. To meet the unique science, curation, and planetary protection needs of MSR, substantial analytical and sample management capabilities would be required in an SRF. Summary-5. Because of the long lead-time for SRF design, construction, and certification, it is important that preparations begin immediately, even if there is delay in the return of samples