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Acidophilic sulphate‐reducing bacteria (aSRB) are widespread anaerobic microorganisms that perform dissimilatory sulphate reduction and have key adaptations to tolerate acidic environments (pH <5.0), such as proton impermeability and Donnan potential. This diverse prokaryotic group is of interest from physiological, ecological, and applicational viewpoints. In this review, we summarize the interactions between aSRB and other microbial guilds, such as syntrophy, and their roles in the biogeochemical cycling of sulphur, iron, carbon, and other elements. We discuss the biotechnological applications of aSRB in treating acid mine drainage (AMD, pH <3), focusing on their ability to produce biogenic sulphide and precipitate metals, particularly in the context of utilizing microbial consortia instead of pure isolates. Metal sulphide nanoparticles recovered after AMD treatment have multiple potential technological uses, including in electronics and biomedicine, contributing to a cost‐effective circular economy. The products of aSRB metabolisms, such as biominerals and isotopes, could also serve as biosignatures to understand ancient and extant microbial life in the universe. Overall, aSRB are active components of the sulphur and carbon cycles under acidic conditions, with potential natural and technological implications for the world around us. [ABSTRACT FROM AUTHOR]

Background: There is increasing recognition of the importance of maximizing program‐setting fit in scaling and spreading effective programs. However, in the context of hospital‐based mobility programs, there is limited information on how settings could consider local context and modify program characteristics or implementation activities to enhance fit. To fill this gap, we examined site‐initiated adaptations to STRIDE, a hospital‐based mobility program for older Veterans, at eight Veterans Affairs facilities across the United States. Methods: STRIDE was implemented at eight hospitals in a stepped‐wedge cluster randomized trial. During the pre‐implementation phase, sites were encouraged to adapt program characteristics to optimize implementation and align with their hospital's resources, needs, and culture. Recommended adaptations included those related to staffing models, marketing, and documentation. To assess the number and types of adaptations, multiple data sources were reviewed, including implementation support notes from site‐level support calls and group‐based learning collaborative sessions. Adaptations were classified based on the Framework for Reporting Adaptations and Modifications‐Enhanced (FRAME), including attention to what was adapted, when, why, and by whom. We reviewed the number and types of adaptations across sites that did and did not sustain STRIDE, defined as continued program delivery during the post‐implementation period. Results: A total of 25 adaptations were reported and classified across seven of the eight sites. Adaptations were reported across five areas: program documentation (n = 13), patient eligibility criteria (n = 5), program enhancements (n = 3), staffing model (n = 2), and marketing and recruitment (n = 2). More than one‐half of adaptations were planned. Adaptations were common in both sustaining and non‐sustaining sites. Conclusions: Adaptations were common within a program designed with flexible implementation in mind. Identifying common areas of planned and unplanned adaptations within a flexible program such as STRIDE may contribute to more efficient and effective national scaling. Future research should evaluate the relationship between adaptations and program implementation. [ABSTRACT FROM AUTHOR]

Understanding the fate of organic carbon in thawed permafrost is crucial for predicting climate feedback. While minerals and microbial necromass are known to play crucial roles in the long‐term stability of organic carbon in subsoils, their exact influence on carbon persistence in Arctic permafrost remains uncertain. Our study, combining radiocarbon dating and biomarker analyses, showed that soil organic carbon in Alaskan permafrost had millennial‐scale radiocarbon ages and contained only 10%–15% microbial necromass carbon, significantly lower than the global average of ~30%–60%. This ancient carbon exhibited a weak correlation with reactive minerals but a stronger correlation with mineral weathering (reactive iron to total iron ratio). Peroxidase activity displayed a high correlation coefficient (p < 10−6) with Δ14C and δ13C, indicating its strong predictive power for carbon persistence. Further, a positive correlation between peroxidase activity and polysaccharides indicates that increased peroxidase activity may promote the protection of plant residues, potentially by fostering the formation of mineral‐organic associations. This protective role of mineral surfaces on biopolymers was further supported by examining 1451 synchrotron radiation infrared spectra from soil aggregates, which revealed a strong correlation between mineral OH groups and organic functional groups at the submicron scale. An incubation experiment revealed that increased moisture contents, particularly within the 0%–40% range, significantly elevated peroxidase activity, suggesting that ancient carbon in permafrost soils is vulnerable to moisture‐induced destabilization. Collectively, this study offers mechanistic insights into the persistence of carbon in thawed permafrost soils, essential for refining permafrost carbon‐climate feedbacks. [ABSTRACT FROM AUTHOR]

In response to the growing number of outbreaks of emerging infectious diseases, the US Administration for Strategic Preparedness and Response (ASPR) has embarked on a plan to improve and expand special pathogen patient care capabilities. To achieve this, ASPR is developing a coordinated network of Regional Emerging Special Pathogen Treatment Centers (RESPTCs) to serve as state-of-the-art facilities staffed by a highly trained workforce to care for and manage special pathogen patients across the lifespan. The RESPTC network represents the operational arm of a broader US National Special Pathogen System of care to prevent and prepare for the next infectious disease outbreak. RESPTCs are strategically located in every region across the country and form a network linking local and regional healthcare partners to enhance national preparedness through training in best practices for detection, isolation, and treatment of individuals suspected of or known to be infected with a special pathogen. This local, regional, and national network is also designed to lead a coordinated response that includes the dissemination of accurate and trustworthy information to responders and the public. The overarching goal of the RESPTCs is to serve as a valuable resource for clinical care, training, and material support to meet current and future major infectious diseases challenges. In this case study, 2 new RESPTCs, MedStar Washington Hospital Center and the University of North Carolina, describe their experiences related to designing a biocontainment unit, creating clinical teams, building staff resiliency, receiving mentoring from regional RESPTC partners, and developing opportunities for innovation. [ABSTRACT FROM AUTHOR]

ABSTRACT The emergence and spread of antimicrobial resistance (AMR) in Gram-negative pathogens, such as carbapenem-resistant Pseudomonas aeruginosa, pose an increasing threat to health care. Patients with immunodeficiencies or chronic pulmonary disease, like cystic fibrosis (CF), are particularly vulnerable to Pseudomonas infections and depend heavily on antibiotic therapy. To broaden limited treatment options, this study evaluated the potency of the recently licensed drugs ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), and cefiderocol (FDC) as well as two novel preclinical antibiotics, darobactins B (DAR B) and B9 (DAR B9), against clinical P. aeruginosa isolates derived from respiratory samples of CF patients. We observed high levels of resistance to all three newly licensed drugs, with cefiderocol exhibiting the best activity. From the 66 investigated P. aeruginosa isolates, a total of 53% were resistant to CZA, 49% to C/T, and 30% to FDC. Strikingly, 52 of the evaluated isolates were obtained from CF patients prior to market introduction of the drugs. Thus, our results suggest that resistance to CZA, C/T, and FDC may be due to preexisting resistance mechanisms. On the other hand, our two novel preclinical compounds performed better than (CZA and C/T) or close to (FDC) the licensed drugs—most likely due to the novel mode of action. Thus, our results highlight the necessity of global consistency in the area of antibiotic stewardship to prevent AMR from further impairing the potency of antibiotics in clinical practice. Ultimately, this study demonstrates the urgency to support the development of novel antimicrobials, preferably with a new mode of action such as darobactins B and B9, two very promising antimicrobial compounds for the treatment of critically ill patients suffering from multidrug-resistant Gram-negative (MRGN) infections. IMPORTANCE Antimicrobial resistance (AMR) represents an ever increasing threat to the health care system. Even recently licensed drugs are often not efficient for the treatment of infections caused by Gram-negative bacteria, like Pseudomonas aeruginosa, a causative agent of lung infections. To address this unmet medical need, innovative antibiotics, which possess a new mode of action, need to be developed. Here, the antibiogram of clinical isolates derived from cystic fibrosis patients was generated and new bicyclic heptapeptides, which inhibit the outer membrane protein BamA, exhibited strong activity, also against multidrug-resistant isolates.

To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cells. We determined the sequence of 3196 MHC class I ligands representing 1921 proteins from a panel of 20 breast cancer cell lines. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2740. Of the unique peptides eluted, more than 1750 had been previously identified, and of these, sixteen have been shown to be immunogenic. Importantly, half of these immunogenic peptides were shared between different breast cancer cell lines. MHC class I binding probability was used to plot the distribution of the eluted peptides in accordance with the binding score for each breast cancer cell line. We also determined that the tested breast cancer cells presented 89 mutation-containing peptides and peptides derived from aberrantly translated genes, 7 of which were shared between four or two different cell lines. Overall, the high throughput identification of MHC class I-loaded peptides is an effective strategy for systematic characterization of cancer peptides, and could be employed for design of multi-peptide anticancer vaccines.SignificanceBy employing proteomic analyses of eluted peptides from breast cancer cells, the current study has built an initial HLA-I-typed antigen collection for breast cancer research. It was also determined that immunogenic epitopes can be identified using established cell lines and that shared immunogenic peptides can be found in different cancer types such as breast cancer and leukemia. Importantly, out of 3196 eluted peptides that included duplicate peptides in different cells 89 peptides either contained mutation in their sequence or were derived from aberrant translation suggesting that mutation-containing epitopes are on the order of 2-3% in breast cancer cells. Finally, our results suggest that interfering with MHC class I function is one of the mechanisms of how tumor cells escape immune system attack.

We have reported that JMJD5 and JMJD7 (JMJD5/7) are responsible for the clipping of arginine methylated histone tails to generate "tailless nucleosomes", which could release the pausing RNA polymerase II (Pol II) into productive transcription elongation. JMJD5/7 function as endopeptidases that cleave histone tails specifically adjacent to methylated arginine residues and continue to degrade N-terminal residues of histones via their aminopeptidase activity. Here, we report structural and biochemical studies on JMJD5/7 to understand the basis of substrate recognition and catalysis mechanism by this JmjC subfamily. Recognition between these enzymes and histone substrates is specific, which is reflected by the binding data between enzymes and substrates. High structural similarity between JMJD5 and JMJD7 is reflected by the shared common substrates and high binding affinity. However, JMJD5 does not bind to arginine methylated histone tails with additional lysine acetylation while JMJD7 does not bind to arginine methylated histone tails with additional lysine methylation. Furthermore, the complex structures of JMJD5 and arginine derivatives revealed a Tudor domain-like binding pocket to accommodate the methylated sidechain of arginine, but not lysine. There also exists a glutamine close to the catalytic center, which may suggest a unique imidic acid mediated catalytic mechanism for proteolysis by JMJD5/7.

We explore the data collected by a 3-component induction coil magnetometer system with respect to motion of the instruments in earths static magnetic field. The sensitivtiy of the inductiuon coil magnetometer leads to unprecediented accuracy on tilt measurements. We model the signals observed during seismic events as being perturbations in coil orientation. In theory, these perturbations can include ground roll, ocean motion, nearby cultural seismicity, or any other field with a tilting effect. Using data from a magnetic observatory near Parkfield CA we invert several time series of coil data during different levels of seismic activity in an attempt to determine the magnitudes of rotation at which our model accurately describes the coil data. Finally, we explore the transfer function between the coils and nearby seismic instruments (accelerometers, tiltmeters, and velocity seismometers).

Rhabdoid tumors (RT) are among the most aggressive tumors in early childhood. Overall survival remains poor, and treatment only effectively occurs at the cost of high toxicity and late adverse effects. It has been reported that the neurokinin-1 receptor/ substance P complex plays an important role in cancer and proved to be a promising target. However, its role in RT has not yet been described. This study aims to determine whether the neurokinin-1 receptor is expressed in RT and whether neurokinin-1 receptor (NK1R) antagonists can serve as a novel therapeutic approach in treating RTs. By in silico analysis using the cBio Cancer Genomics Portal we found that RTs highly express neurokinin-1 receptor. We confirmed these results by RT-PCR in both tumor cell lines and in human tissue samples of various affected organs. We demonstrated a growth inhibitory and apoptotic effect of aprepitant in viability assays and flow cytometry. Furthermore, this effect proved to remain when used in combination with the cytostatic cisplatin. Western blot analysis showed an upregulation of apoptotic signaling pathways in rhabdoid tumors when treated with aprepitant. Overall, our findings suggest that NK1R may be a promising target for the treatment of RT in combination with other anti-cancer therapies and can be targeted with the NK1R antagonist aprepitant.

A produção de carvão vegetal é uma atividade tradicional realizada em pequenas propriedades rurais em muitas áreas do estado. É uma atividade tradicional, pois o conhecimento é intergeracional. Além disso, é uma fonte significativa de renda para várias famílias. No entanto, como a produção aumentou junto com a expansão urbana e os métodos de produção mantiveram-se rudimentares, estão causando tensões e problemas de saúde. Como exemplo, os fornos tradicionais geram em média 600 kg de vapores de pirólise por dia, o que dificulta a remoção dos vapores com uma filtragem simples. Foram feitos esforços empíricos para reduzir os impactos negativos, como a combinação de queimadores nos fornos, embora com resultados limitados. Portanto, a compreensão científica do processo é necessária para que as ações projetadas sejam executadas. Este trabalho procura contribuir para a identificação dos aspectos ambientais mais significativos e permite a estruturação de um plano de ação para reduzir os impactos da produção de carvão vegetal. O trabalho exposto é um estudo de caso realizado em uma carvoaria na cidade de Ivoti, no Estado do Rio Grande do Sul.

Anthropogenic activities are modifying the oceanic environment rapidly and are causing ocean warming and deoxygenation, affecting biodiversity, productivity, and biogeochemical cycling. In coastal sediments, anaerobic organic matter degradation essentially fuels the production of hydrogen sulfide and methane. The release of these compounds from sediments is detrimental for the (local) environment and entails socio-economic consequences. Therefore, it is vital to understand which microbes catalyze the re-oxidation of these compounds under environmental dynamics, thereby mitigating their release to the water column. Here we use the seasonally dynamic Boknis Eck study site (SW Baltic Sea), where bottom waters annually fall hypoxic or anoxic after the summer months, to extrapolate how the microbial community and its activity reflects rising temperatures and deoxygenation. During October 2018, hallmarked by warmer bottom water and following a hypoxic event, modeled sulfide and methane production and consumption rates are higher than in March at lower temperatures and under fully oxic bottom water conditions. The microbial populations catalyzing sulfide and methane metabolisms are found in shallower sediment zones in October 2018 than in March 2019. DNA-and RNA profiling of sediments indicate a shift from primarily organotrophic to (autotrophic) sulfide oxidizing Bacteria, respectively. Previous studies using data collected over decades demonstrate rising temperatures, decreasing eutrophication, lower primary production and thus less fresh organic matter transported to the Boknis Eck sediments. Elevated temperatures are known to stimulate methanogenesis, anaerobic oxidation of methane, sulfate reduction and essentially microbial sulfide consumption, likely explaining the shift to a phylogenetically more diverse sulfide oxidizing community based on RNA.

Using portraiture methodology involving interview, observation, and artifact data, this study portrays a turnaround leader, Dr. Susan Gray, in a high needs, rural district in the Southeast. In three years, Gray led Lincoln Elementary from nearly being reconstituted to being an award-winning school. Gray has subsequently been assigned other leadership roles that required a change agent. The study narrates Gray's professional arc, highlighting her drive, ability to build relational trust, unapologetic disruption of deficit thinking, mission-orientation, and high expectations to guide the turnaround process. The paper concludes with implications for practice and research related to leadership preparation and school turnaround.

In the United States, policies in forty states and D.C. incorporate student growth measures--estimates of student progress attributed to educators--into educator evaluation. The federal government positions such policies as levers for ensuring that more students are taught by effective teachers and that effective educators are more equitably distributed amongst schools. Because these policies are new, little is known about how educators respond to them. Mixed methods survey data from a large, diverse district in North Carolina, a state that incorporates value-added data into teacher evaluations, indicate that substantive, unintended effects may undermine the purposes for which these policies were developed. Results indicate that educators evaluated by value-added are generally opposed to its use. Those who have previously been evaluated by value-added have significantly more negative perceptions about the fairness and accuracy of value-added, are more opposed to its use in educator evaluation, and are more likely to perceive that it will not result in more equitable distribution of good educators across schools and that educators will avoid working with certain students because of value-added. Respondents perceived effects of the use of value-added for teacher accountability that fall within five themes: 1) Educators increasingly game the system and teach to the test, 2) Teachers increasingly leave the field, 3) Some educators seek to avoid working with certain students and at certain schools, 4) Educators feel an increase in stress, pressure, and anxiety, 5) Educator collaboration is decreasing, and competition is increasing. Based on findings, the author recommends five mid-course policy corrections.