Leveraging legacy archaeological collections as proxies for climate and environmental research.

Understanding the causes and consequences of previous climate changes is essential for testing present-day climate models and projections. Archaeological sites are paleoenvironmental archives containing unique ecological baselines with data on paleoclimate transformations at a human timescale. Anthropogenic and nonanthropogenic forces have destroyed many sites, and others are under immediate threat. In the face of this loss, previously excavated collections from these sites-referred to as legacy collections-offer a source of climate and other paleoenvironmental information that may no longer exist elsewhere. Here, we 1) review obstacles to systematically using data from legacy archaeological collections, such as inconsistent or unreported field methods, inadequate records, unsatisfactory curation, and insufficient public knowledge of relevant collections; 2) suggest best practices for integrating archaeological data into climate and environmental research; and 3) summarize several studies to demonstrate the benefits and challenges of using legacy collections as archives of local and regional environmental proxies. Data from archaeological legacy collections contribute regional ecological baselines as well as serve to correct shifting baselines. They also enable regional climate reconstructions at various timescales and corroborate or refine radiocarbon dates. Such uses of legacy collections raise ethical concerns regarding ownership of and responsibility for cultural resources and highlight the importance of Indigenous involvement in planning and executing fieldwork and stewardship of cultural heritage. Finally, we discuss methodologies, practices, and policies pertaining to archaeological legacy collections and support calls for discipline-wide shifts in collections management to ensure their long-term utility in multidisciplinary research and public engagement.

Cognitive Decline, Cerebral-Spleen Tryptophan Metabolism, Oxidative Stress, Cytokine Production, and Regulation of the Txnip Gene in a Triple Transgenic Mouse Model of Alzheimer Disease.

Pathologic inflammation in response to injury, infection, or oxidative stress is a proposed mechanism relating cognitive decline to dementia. The kynurenine pathway and thioredoxin-interacting protein (TXNIP) activity regulate inflammation and neurotoxicity in Alzheimer disease (AD). We examined cognitive deficits, kynurenine pathway mediators, TXNIP, and oxidative damage in the cerebrum and spleen, including inflammatory cytokine production by stimulated splenocytes, from female triple transgenic (3xTg-AD) mice in early and late stages of disease progression, and characterized tissue-specific epigenetic regulation of Txnip gene expression. We show that cognitive deficits in 7-month-old 3xTg-AD mice are associated with a stable increase in cerebrum and spleen tryptophan metabolites, with a concomitant increase in amyloid ß 40 (Aß40)/Aß42 and tau/hyperphosphorylated tau pathologies and a coordinated reduction in spleen proinflammatory cytokine production in 17-month-old mice. The enhanced cerebrum TXNIP expression is associated with increased histone acetylation, transcription factor [Aß42 or CCCTC-binding factor (CTCF)] binding, and Txnip promoter hypomethylation, whereas the attenuated spleen TXNIP expression is associated with increased histone methylation, reduced CTCF binding, and Txnip promoter hypermethylation. These results suggest a causal relationship among epigenomic state, TXNIP expression, cerebral-spleen tryptophan metabolism, inflammatory cytokine production, and cognitive decline; and they provide a potential mechanism for Txnip gene regulation in normal and pathologic conditions, suggesting TXNIP levels may be a useful predictive or diagnostic biomarker for Aß40/Aß42 targeted AD therapies.

Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.

MtmOIV and MtmW catalyze the final two reactions in the mithramycin (MTM) biosynthetic pathway, the Baeyer-Villiger opening of the fourth ring of premithramycin B (PMB), creating the C3 pentyl side chain, strictly followed by reduction of the distal keto group on the new side chain. Unexpectedly this results in a C2 stereoisomer of mithramycin, iso-mithramycin (iso-MTM). Iso-MTM undergoes a non-enzymatic isomerization to MTM catalyzed by Mg2+ ions. Crystal structures of MtmW and its complexes with co-substrate NADPH and PEG, suggest a catalytic mechanism of MtmW. The structures also show that a tetrameric assembly of this enzyme strikingly resembles the ring-shaped ß subunit of a vertebrate ion channel. We show that MtmW and MtmOIV form a complex in the presence of PMB and NADPH, presumably to hand over the unstable MtmOIV product to MtmW, yielding iso-MTM, as a potential self-resistance mechanism against MTM toxicity.

The use of a Foley balloon catheter to control junctional hemorrhage in a dog with severe vascular injury secondary to penetrating trauma.

INTRODUCTION: Penetrating trauma is commonly seen in dogs. The severity depends on the site of injury and tissue involved. Junctional hemorrhage can be especially challenging to control given the inaccessibility of the damaged vasculature. Methods described to control life-threatening hemorrhage in dogs include direct pressure, hemostatic gauze, hemostatic powder or granules, wound packing, tourniquets, and direct clamping of the vasculature. Foley balloon catheters (FBC) are commonly used to tamponade deep vascular hemorrhage in people, but the technique has not been previously described in the veterinary literature. OBJECTIVE: To present a case of penetrating trauma (bite wound) in a dog with a transected left femoral artery and vein in which the life-threatening hemorrhage was initially controlled with tamponade using an FBC. CASE: A 7-year-old neutered male Terrier mix presented in hemorrhagic shock with an Animal Trauma Triage (ATT) of 7 and modifed Glasgow coma scale (MGCS) of 17 forty-five minutes after being attacked by another dog. The dog had sustained a deep penetrating wound to the left groin. Direct pressure and gauze packing at the site of injury were not successful at slowing the hemorrhage. A 10-Fr, 55-cm Foley catheter with a 5-mL balloon was inserted into the wound tract, and the balloon was inflated with 7.5 mL of sterile saline. Hemorrhage was controlled after inflation of the Foley balloon. CBC, blood biochemistries, abdominal point-of-care ultrasound, radiographs, prothrombin time, partial thromboplastin time, and whole blood viscoelastic testing were performed. Stabilization included fluid resuscitation, analgesics, antimicrobials, and epsilon aminocaproic acid. The dog was then anesthetized to definitively identify and control the hemorrhage. Transection of the left femoral artery and vein where identified and ligated. The dog fully recovered and was discharged 32 hours later. NEW AND UNIQUE INFORMATION: FBCs may be useful as an alternative technique for temporary control of life-threatening hemorrhage secondary to penetrating injuries in both the emergency department and prehospital settings.

Stress and the Emerging Roles of Chromatin Remodeling in Signal Integration and Stable Transmission of Reversible Phenotypes.

The influence of early life experience and degree of parental-infant attachment on emotional development in children and adolescents has been comprehensively studied. Structural and mechanistic insight into the biological foundation and maintenance of mammalian defensive systems (metabolic, immune, nervous and behavioral) is slowly advancing through the emerging field of developmental molecular (epi)genetics. Initial evidence revealed that differential nurture early in life generates stable differences in offspring hypothalamic-pituitary-adrenal (HPA) regulation, in part, through chromatin remodeling and changes in DNA methylation of specific genes expressed in the brain, revealing physical, biochemical and molecular paths for the epidemiological concept of gene-environment interactions. Herein, a primary molecular mechanism underpinning the early developmental programming and lifelong maintenance of defensive (emotional) responses in the offspring is the alteration of chromatin domains of specific genomic regions from a condensed state (heterochromatin) to a transcriptionally accessible state (euchromatin). Conversely, DNA methylation promotes the formation of heterochromatin, which is essential for gene silencing, genomic integrity and chromosome segregation. Therefore, inter-individual differences in chromatin modifications and DNA methylation marks hold great potential for assessing the impact of both early life experience and effectiveness of intervention programs-from guided psychosocial strategies focused on changing behavior to pharmacological treatments that target chromatin remodeling and DNA methylation enzymes to dietary approaches that alter cellular pools of metabolic intermediates and methyl donors to affect nutrient bioavailability and metabolism. In this review article, we discuss the potential molecular mechanism(s) of gene regulation associated with chromatin modeling and programming of endocrine (e.g., HPA and metabolic or cardiovascular) and behavioral (e.g., fearfulness, vigilance) responses to stress, including alterations in DNA methylation and the role of DNA repair machinery. From parental history (e.g., drugs, housing, illness, nutrition, socialization) to maternal-offspring exchanges of nutrition, microbiota, antibodies and stimulation, the nature of nurture provides not only mechanistic insight into how experiences propagate from external to internal variables, but also identifies a composite therapeutic target, chromatin modeling, for gestational/prenatal stress, adolescent anxiety/depression and adult-onset neuropsychiatric disease.

Population and genomic analysis of the genus Halorubrum.

The Halobacteria are known to engage in frequent gene transfer and homologous recombination. For stably diverged lineages to persist some checks on the rate of between lineage recombination must exist. We surveyed a group of isolates from the Aran-Bidgol endorheic lake in Iran and sequenced a selection of them. Multilocus Sequence Analysis (MLSA) and Average Nucleotide Identity (ANI) revealed multiple clusters (phylogroups) of organisms present in the lake. Patterns of intein and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) presence/absence and their sequence similarity, GC usage along with the ANI and the identities of the genes used in the MLSA revealed that two of these clusters share an exchange bias toward others in their phylogroup while showing reduced rates of exchange with other organisms in the environment. However, a third cluster, composed in part of named species from other areas of central Asia, displayed many indications of variability in exchange partners, from within the lake as well as outside the lake. We conclude that barriers to gene exchange exist between the two purely Aran-Bidgol phylogroups, and that the third cluster with members from other regions is not a single population and likely reflects an amalgamation of several populations.

Evidence from phylogenetic and genome fingerprinting analyses suggests rapidly changing variation in Halorubrum and Haloarcula populations.

Halobacteria require high NaCl concentrations for growth and are the dominant inhabitants of hypersaline environments above 15% NaCl. They are well-documented to be highly recombinogenic, both in frequency and in the range of exchange partners. In this study, we examine the genetic and genomic variation of cultured, naturally co-occurring environmental populations of Halobacteria. Sequence data from multiple loci (~2500 bp) identified many closely and more distantly related strains belonging to the genera Halorubrum and Haloarcula. Genome fingerprinting using a random priming PCR amplification method to analyze these isolates revealed diverse banding patterns across each of the genera and surprisingly even for isolates that are identical at the nucleotide level for five protein coding sequenced loci. This variance in genome structure even between identical multilocus sequence analysis (MLSA) haplotypes indicates that accumulation of genomic variation is rapid: faster than the rate of third codon substitutions.