Complete Genomic Characterization of a Pathogenic A.II Strain of Francisella tularensis Subspecies tularensis

Francisella tularensis is the causative agent of tularemia, which is a highly lethal disease from nature and potentially from a biological weapon. This species contains four recognized subspecies including the North American endemic F. tularensis subsp. tularensis (type A), whose genetic diversity is correlated with its geographic distribution including a major population subdivision referred to as A.I and A.II. The biological significance of the A.I – A.II genetic differentiation is unknown, though there are suggestive ecological and epidemiological correlations. In order to understand the differentiation at the genomic level, we have determined the complete sequence of an A.II strain (WY96-3418) and compared it to the genome of Schu S4 from the A.I population. We find that this A.II genome is 1,898,476 bp in size with 1,820 genes, 1,303 of which code for proteins. While extensive genomic variation exists between “WY96” and Schu S4, there is only one whole gene difference. This one gene difference is a hypothetical protein of unknown function. In contrast, there are numerous SNPs (3,367), small indels (1,015), IS element differences (7) and large chromosomal rearrangements (31), including both inversions and translocations. The rearrangement borders are frequently associated with IS elements, which would facilitate intragenomic recombination events. The pathogenicity island duplicated regions (DR1 and DR2) are essentially identical in WY96 but vary relative to Schu S4 at 60 nucleotide positions. Other potential virulence-associated genes (231) varied at 559 nucleotide positions, including 357 non-synonymous changes. Molecular clock estimates for the divergence time between A.I and A.II genomes for different chromosomal regions ranged from 866 to 2131 years before present. This paper is the first complete genomic characterization of a member of the A.II clade of Francisella tularensis subsp. tularensis

The Pathogenomic Sequence Analysis of B. cereus and B. Thuringiensis isolates closely related to Bacillus anthracis

The sequencing and analysis of two close relatives of Bacillus anthracis are reported. AFLP analysis of over 300 isolates of B. cereus, B. thuringiensis and B. anthracis identified two isolates as being very closely related to B. anthracis. One, a B. cereus, BcE33L, was isolated from a zebra carcass in Nambia; the second, a B. thuringiensis, 97-27, was isolated from a necrotic human wound. The B. cereus appears to be the closest anthracis relative sequenced to date. A core genome of over 3,900 genes was compiled for the Bacillus cereus group, including B anthracis. Comparative analysis of these two genomes with other members of the B. cereus group provides insight into the evolutionary relationships among these organisms. Evidence is presented that differential regulation modulates virulence, rather than simple acquisition of virulence factors. These genome sequences provide insight into the molecular mechanisms contributing to the host range and virulence of this group of organisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Grand Challenges for Biological and Environmental Research: A Long-Term Vision

The interactions and feedbacks among plants, animals, microbes, humans, and the environment ultimately form the world in which we live. This world is now facing challenges from a growing and increasingly affluent human population whose numbers and lifestyles are driving ever greater energy demand and impacting climate. These and other contributing factors will make energy and climate sustainability extremely difficult to achieve over the 20-year time horizon that is the focus of this report. Despite these severe challenges, there is optimism that deeper understanding of our environment will enable us to mitigate detrimental effects, while also harnessing biological and climate systems to ensure a sustainable energy future. This effort is advanced by scientific inquiries in the fields of atmospheric chemistry and physics, biology, ecology, and subsurface science - all made possible by computing. The Office of Biological and Environmental Research (BER) within the Department of Energy's (DOE) Office of Science has a long history of bringing together researchers from different disciplines to address critical national needs in determining the biological and environmental impacts of energy production and use, characterizing the interplay of climate and energy, and collaborating with other agencies and DOE programs to improve the world's most powerful climate models. BER science focuses on three distinct areas: (1) What are the roles of Earth system components (atmosphere, land, oceans, sea ice, and the biosphere) in determining climate? (2) How is the information stored in a genome translated into microbial, plant, and ecosystem processes that influence biofuel production, climate feedbacks, and the natural cycling of carbon? (3) What are the biological, geochemical, and physical forces that govern the behavior of Earth's subsurface environment? Ultimately, the goal of BER science is to support experimentation and modeling that can reliably predict the outcomes and behaviors of complex biological and environmental systems, leading to robust solutions for DOE missions and strategic goals. In March 2010, the Biological and Environmental Research Advisory Committee held the Grand Challenges for Biological and Environmental Research: A Long-Term Vision workshop to identify scientific opportunities and grand challenges for BER science in the coming decades and to develop an overall strategy for drafting a long-term vision for BER. Key workshop goals included: (1) Identifying the greatest scientific challenges in biology, climate, and the environment that DOE will face over a 20-year time horizon. (2) Describing how BER should be positioned to address those challenges. (3) Determining the new and innovative tools needed to advance BER science. (4) Suggesting how the workforce of the future should be trained in integrative system science. This report lays out grand research challenges for BER - in biological systems, climate, energy sustainability, computing, and education and workforce training - that can put society on a path to achieve the scientific evidence and predictive understanding needed to inform decision making and planning to address future energy needs, climate change, water availability, and land use

Traumatic brain injury provokes low fibrinolytic activity in severely injured patients

BACKGROUNDTraumatic brain injury (TBI) in combination with shock has been associated with hypocoagulability. However, recent data suggest that TBI itself can promote a systemic procoagulant state via the release of brain-derived extracellular vesicles. The objective of our study was to identify if TBI was associated with differences in thrombelastography indices when controlling for other variables associated with coagulopathy following trauma. We hypothesized that TBI is independently associated with a less coagulopathic state. METHODSProspective study includes all highest-level trauma activations at an urban Level I trauma center, from 2014 to 2020. Traumatic brain injury was defined as Abbreviated Injury Scale head score greater than 3. Blood samples were drawn at emergency department admission. Linear regression was used to assess the role of independent predictors on trauma induced coagulopathy. Models adjusted for Injury Severity Score (ISS), shock (defined as ED SBP108, or first hospital base deficit >10), and prehospital Glasgow Coma Scale score. RESULTSOf the 1,023 patients included, 291 (28%) suffered a TBI. Traumatic brain injury patients more often were female (26% vs. 19%, p = 0.01), had blunt trauma (83% vs. 43%, p < 0.0001), shock (33% vs. 25%, p = 0.009), and higher median ISS (29 vs. 10, p < 0.0001). Fibrinolysis shutdown (25% vs. 18%) was more common in the TBI group (p < 0.0001). When controlled for the confounding effects of ISS and shock, the presence of TBI independently decreases lysis at 30 minutes (LY30) (beta estimate: -0.16 ± 0.06, p = 0.004). This effect of TBI on LY30 persisted when controlling for sex and mechanism of injury in addition to ISS and shock (beta estimate: -0.13 ± 0.06, p = 0.022). CONCLUSIONTraumatic brain injury is associated with lower LY30 independent of shock, tissue injury, sex, and mechanism of injury. These findings suggest a propensity toward a hypercoagulable state in patients with TBI, possibly due to fibrinolysis shutdown. LEVEL OF EVIDENCEPrognostic and Epidemiologic; Level III

Mind the Sustainability Gap

Despite increasing efforts to reach sustainability, key global biophysical indicators such as climate change and biodiversity loss continue to deteriorate rather than improve. Ongoing failure to move towards sustainability calls into question the focus of current research and policy. We recommend two strategies for progress. First, sustainability must be conceptualized as a hierarchy of considerations, with the biophysical limits of the Earth setting the ultimate boundaries within which social and economic goals must be achieved. Second, transdisciplinary research programs must confront key normative questions facing modern consumer societies. The humanities should have a key role in such programs. Assisted by these strategies, ambitious targets that realistically reflect the biophysical limits of the life-support system of the Earth must be set and relentlessly worked towards

Electrical Burns During Fruit Harvesting

Electrocutions during tree trimming or fruit harvesting are occasionally reported in the public media, but the actual incidence is unknown. Some fruit trees (eg, mango and avocado) can exceed 30 feet, with dense foliage concealing the fruit and overlying power lines so burns associated with harvesting these fruits are often exacerbated with falls. However, there are limited data on this subject. To fill this gap, we provide some of the first information on this unique injury pattern. All electrocutions from 2013 to 2018 were retrospectively reviewed at an ABA-verified burn center. Demographics, injury patterns, and complications were analyzed. Of 97 electrocutions, 22 (23%) were associated with fruit procurement. This population was aged 43 ± 14 years, 95% (n = 21) male, injury severity score of 15 ± 13, and total body surface area burned 4% [1%-9%]. Third-degree burns were present in 36% (n = 8). ICU admission was required in 59% (n = 13) and 39% of the survivors required operative interventions for the burn. Compartment syndrome occurred in 18% (n = 4) and 14% (n = 3) patients required amputations. Falls complicated the care in 50% (n = 11), with associated head, chest, and/or extremity trauma. Mortality was 32% (n = 7), with three patients presenting dead on arrival. All but 3 injuries occurred between June and December, coinciding with mango and avocado season. Electrocution during fruit picking is a seasonal injury often exacerbated by falls. Management is challenging, and favorable outcome depends on recognition of the complexity of the polytrauma

Advanced Surgical Skills for Exposure in Trauma (ASSET) course improves military surgeon confidence

Active duty military surgeons often have limited trauma surgery experience prior to deployment. Consequently, military-civilian training programs have been developed at high-volume trauma centers to evaluate and maintain proficiencies. Advanced Surgical Skills for Exposure in Trauma (ASSET) was incorporated into the predeployment curriculum at the Army Trauma Training Detachment in 2011. This is the first study to assess whether military surgeons demonstrated improved knowledge and increased confidence after taking ASSET. Retrospective cohort study. Quaternary care hospital. Attending military surgeons who completed ASSET between July 2011 and October 2020. Pre- and post-course self-reported comfort level with procedures was converted from a five-point Likert scale to a percentage and compared using paired t-tests. In 188 military surgeons, the median time in practice was 3 (1-8) years, with specialties in general surgery (52 percent), orthopedic surgery (29 percent), trauma (7 percent), and other disciplines (12 percent). The completed self-evaluation response rate was 80 percent (n = 151). The self-reported comfort level for all body regions improved following course completion (p < 0.001): chest (27 percent), neck (23 percent), upper extremity (22 percent), lower extremity (21 percent), and abdomen/pelvis (19 percent). The overall score on the competency test improved after completion of ASSET, with averages increasing from 62 ± 18 percent pretest to 71 ± 13 percent post-test (p < 0.001). After taking the ASSET course, military surgeons demonstrated improved knowledge and increased confidence in the operative skills taught in the course. The ASSET course may provide sustainment of knowledge and confidence if used at regular intervals to maintain trauma skills and deployment readiness