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Antimicrobial resistance (AMR), arising from decades of imprudent anthropogenic use of antimicrobials in healthcare and agriculture, is considered one of the greatest One Health crises facing healthcare globally. Antimicrobial pollutants released from human-associated sources are intensifying resistance evolution in the environment. Due to various ecological factors, wildlife interact with these polluted ecosystems, acquiring resistant bacteria and genes. Although wildlife are recognized reservoirs and disseminators of AMR in the environment, current AMR surveillance systems still primarily focus on clinical and agricultural settings, neglecting this environmental dimension. Wildlife can serve as valuable sentinels of AMR in the environment, reflecting ecosystem health, and the effectiveness of mitigation strategies. This review explores knowledge gaps surrounding the ecological factors influencing AMR acquisition and dissemination in wildlife, and highlights limitations in current surveillance systems and policy instruments that do not sufficiently address the environmental component of AMR. We discuss the underutilized opportunity of using wildlife as sentinel species in a holistic, One Health-centred AMR surveillance system. By better integrating wildlife into systematic AMR surveillance and policy, and leveraging advances in high-throughput technologies, we can track and predict resistance evolution, assess the ecological impacts, and better understand the complex dynamics of environmental transmission of AMR across ecosystems., (© The Author(s) 2025. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: Glioblastoma (GBM) is the most aggressive primary brain malignancy with <45% living a year beyond diagnosis. Previously published investigations of long-term survivors (LTS) provided clinical data but rarely incorporated a comprehensive clinical and molecular analysis. Herein, we identify clinical, imaging, molecular, and outcome features for 23 GBM-LTS patients and compare them with a matched cohort of short-term survivors (STS)., Methods: Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients living ≥3 years post-diagnosis ( N LTS  = 23) or <3 years ( N STS  = 75) were identified from our Natural History study. Clinical and demographic characteristics were compared. Tumor tissue was analyzed with targeted next generation sequencing (NGS) ( N LTS  = 23; N STS  = 74) and methylation analysis ( N LTS  = 18; N STS  = 28). Pre-surgical MRI scans for a subset of LTS ( N  = 14) and STS control (N = 28) matched on sex, age, and extent of resection were analyzed., Results: LTS tended to be younger. Diagnostic MRIs showed more LTS with T1 tumor hypointensity. LTS tumors were enriched for MGMT p methylation and tumor protein 53 ( TP53 ) mutation. Three patients with classic GBM histology were reclassified based on NGS and methylation testing. Additionally, there were LTS with typical poor prognostic molecular markers., Conclusions: Our findings emphasize that generalized predictions of prognosis are inaccurate for individual patients and underscore the need for complete clinical evaluation including molecular work-up to confirm the diagnosis. Continued accrual of patients to LTS registries that containcomprehensive clinical, imaging, tumor molecular data, and outcomes measures may pro\vide important insights about individual patient prognosis., Competing Interests: None declared., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Sleep disturbance (SD) is common in patients with cancer and has been associated with worse clinical outcomes. This cross-sectional study explored the prevalence of SD in a primary brain tumor (PBT) population, identified associated demographic and clinical characteristics, and investigated co-occurrence of SD with other symptoms and mood disturbance., Methods: Demographic, clinical characteristics, MD Anderson Symptom Inventory-Brain Tumor, and Patient Reported Outcome Measurement Information System Depression and Anxiety Short-Forms were collected from PBT patients at study entry. Descriptive statistics, Chi-square tests, and independent t -tests were used to report results., Results: The sample included 424 patients (58% male, 81% Caucasian) with a mean age of 49 years (range 18-81) and 58% with high-grade gliomas. Moderate-severe SD was reported in 19% of patients and was associated with younger age, poor Karnofsky Performance Status, tumor progression on MRI, and active corticosteroid use. Those with moderate-severe SD had higher overall symptom burden and reported more moderate-severe symptoms. These individuals also reported higher severity in affective and mood disturbance domains, with 3 to 4 times higher prevalence of depressive and anxiety symptoms, respectively. The most frequently co-occurring symptoms with SD were, drowsiness, and distress, though other symptoms typically associated with tumor progression also frequently co-occurred., Conclusions: PBT patients with moderate-severe SD are more symptomatic, have worse mood disturbance, and have several co-occurring symptoms. Targeting interventions for sleep could potentially alleviate other co-occurring symptoms, which may improve life quality for PBT patients. Future longitudinal work examining objective and detailed subjective sleep reports, as well as underlying genetic risk factors, will be important., (Published by Oxford University Press 2022.)

Background: Primary central nervous system (CNS) tumors are often associated with high symptom burden and a poor prognosis from the time of diagnosis. The purpose of this study is to describe patient-reported outcomes (PRO) data from long-term survivors (LTS; ≥5-year survival post-diagnosis)., Methods: Clinical/treatment/molecular characteristics and PROs (symptom burden/interference (MDASI-BT/SP), perceived cognition (Neuro-QoL), anxiety/depression (PROMIS), and general health status (EQ-5D-3L)) were collected on 248 adult LTS between 9/2016 and 8/2019. Descriptive statistics and regression analysis were used to report results., Results: Participants had a median age of 47 years (19-82) and were primarily White (83%) males (51%) with high-grade tumors (59%) and few mutations. Forty-two percent of the 222 brain tumor LTS reported no moderate-to-severe symptoms, whereas 45% reported three or more; most common symptoms were fatigue (40%), difficulty remembering (29%), and drowsiness (28%). Among spine tumor LTS (n = 42), nearly half reported moderate-to-severe weakness, pain, fatigue, and numbness/tingling, with 72% experiencing activity-related interference. Severe anxiety, depression, and cognitive symptoms were reported in up to 23% of the sample. Brain tumor LTS at higher risk for severe symptoms were more likely to be young, unemployed, and have poor KPS (Karnofsky Performance Status), whereas high symptom-risk spinal cord tumor LTS had poor KPS and received any tumor treatment., Conclusions: Findings indicate LTS fall into distinct cohorts with no significant symptoms or very high symptom burden, regardless of tumor grade or mutational profile. These LTS data demonstrate the need for survivorship care programs and future studies to explore the symptom trajectory of all CNS tumor patients for prevention and early interventions., (Published by Oxford University Press 2021.)

Clues to the evolutionary steps producing innovations in oxygenic photosynthesis may be preserved in the genomes of organisms phylogenetically placed between non-photosynthetic Vampirovibrionia (formerly Melainabacteria) and the thylakoid-containing Cyanobacteria. However, only two species with published genomes are known to occupy this phylogenetic space, both within the genus Gloeobacter. Here, we describe nearly complete, metagenome-assembled genomes (MAGs) of an uncultured organism phylogenetically placed near Gloeobacter, for which we propose the name Candidatus Aurora vandensis {Au'ro.ra. L. fem. n. aurora, the goddess of the dawn in Roman mythology; van.de'nsis. N.L. fem. adj. vandensis of Lake Vanda, Antarctica}. The MAG of A. vandensis contains homologs of most genes necessary for oxygenic photosynthesis including key reaction center proteins. Many accessory subunits associated with the photosystems in other species either are missing from the MAG or are poorly conserved. The MAG also lacks homologs of genes associated with the pigments phycocyanoerethrin, phycoeretherin and several structural parts of the phycobilisome. Additional characterization of this organism is expected to inform models of the evolution of oxygenic photosynthesis.

Cucumber beetles, Acalymma vittatum (F.) and Diabrotica undecipunctata howardi (Barber), are specialist herbivores of cucurbits and the vector of Erwinia tracheiphila (E.F. Smith) Holland, the causative agent of wilt disease. Cucumber beetles transmit E. tracheiphila when infected frass falls onto leaf wounds at the site of beetle feeding. We show that E. tracheiphila also can be transmitted via the floral nectaries of Cucurbita pepo ssp. texana L. Andres (Texas gourd). Under field conditions, we found that beetles aggregate in flowers in the late morning, that these beetles chew the anther filaments that cover the nectaries in male flowers thereby exposing the nectary, and that beetle frass accumulates on the nectary. We use real-time polymerase chain reaction to show that most of the flowers produced during the late summer possess beetle frass containing E. tracheiphila. Greenhouse experiments, in which cultures of E. tracheiphila are deposited onto floral nectaries, show that Texas gourds can contract wilt disease through the floral nectaries. Finally, we use green fluorescent protein-transformed E. tracheiphila to document the movement of E. tracheiphila through the nectary into the xylem of the pedicel before the abscission of the flower. Together, these data show that E. tracheiphila can be transmitted through infected frass that falls on or near the floral nectaries. We hypothesize that the concentration of frass from many beetles in the flowers increases both exposure to and the concentration of E. tracheiphila and plays a major role in the dynamics of wilt disease in both wild populations and cultivated squash fields.

Haemangioblastomas of the CNS are a cardinal feature of von Hippel-Lindau (VHL) disease, a dominantly inherited multisystem familial cancer syndrome caused by germline mutation of the VHL tumour suppressor gene. We investigated the frequency of VHL mutations in 188 patients presenting with a single haemangioblastoma, no family history of VHL disease and no evidence of retinal or abdominal manifestations of the disease at the time of diagnosis. We found that approximately 4% of patients had a detectable VHL mutation and all of these cases presented age 40 years or less. Although the identification of a germline VHL mutation has important consequences for the patient (e.g. risk of further CNS and extra-CNS tumours) and their relatives, four patients had germline VHL missense mutations [C162Y, D179N and R200W (two patients)] that may represent haemangioblastoma-only and/or low penetrance mutations. Approximately 5% of patients without a detectable VHL mutation subsequently developed a further 'VHL type tumour' (in most cases a further CNS haemangioblastoma). These findings suggest that a subset of patients with apparently sporadic CNS haemangioblastoma will have a germline VHL mutation but may not be at risk for developing classical VHL disease and a further group may be mosaic for a germline VHL mutation that cannot be detected in blood cells.

The Chloroplast Genome Database (ChloroplastDB) is an interactive, web-based database for fully sequenced plastid genomes, containing genomic, protein, DNA and RNA sequences, gene locations, RNA-editing sites, putative protein families and alignments (http://chloroplast.cbio.psu.edu/). With recent technical advances, the rate of generating new organelle genomes has increased dramatically. However, the established ontology for chloroplast genes and gene features has not been uniformly applied to all chloroplast genomes available in the sequence databases. For example, annotations for some published genome sequences have not evolved with gene naming conventions. ChloroplastDB provides unified annotations, gene name search, BLAST and download functions for chloroplast encoded genes and genomic sequences. A user can retrieve all orthologous sequences with one search regardless of gene names in GenBank. This feature alone greatly facilitates comparative research on sequence evolution including changes in gene content, codon usage, gene structure and post-transcriptional modifications such as RNA editing. Orthologous protein sets are classified by TribeMCL and each set is assigned a standard gene name. Over the next few years, as the number of sequenced chloroplast genomes increases rapidly, the tools available in ChloroplastDB will allow researchers to easily identify and compile target data for comparative analysis of chloroplast genes and genomes.

The combined processes of gene duplication, nucleotide substitution, domain duplication, and intron/exon shuffling can generate a complex set of related genes that may differ substantially in their expression patterns and functions. The APETALA2-like (AP2-like) gene family exhibits patterns of both gene and domain duplication, coupled with changes in sequence, exon arrangement, and expression. In angiosperms, these genes perform an array of functions including the establishment of the floral meristem, the specification of floral organ identity, the regulation of floral homeotic gene expression, the regulation of ovule development, and the growth of floral organs. To determine patterns of gene diversification, we conducted a series of broad phylogenetic analyses of AP2-like sequences from green plants. These studies indicate that the AP2 domain was duplicated prior to the divergence of the two major lineages of AP2-like genes, euAP2 and AINTEGUMENTA (ANT). Structural features of the AP2-like genes as well as phylogenetic analyses of nucleotide and amino acid (aa) sequences of the AP2-like gene family support the presence of the two major lineages. The ANT lineage is supported by a 10-aa insertion in the AP2-R1 domain and a 1-aa insertion in the AP2-R2 domain, relative to all other members of the AP2-like family. MicroRNA172-binding sequences, the function of which has been studied in some of the AP2-like genes in Arabidopsis, are restricted to the euAP2 lineage. Within the ANT lineage, the euANT lineage is characterized by four conserved motifs: one in the 10-aa insertion in the AP2-R1 domain (euANT1) and three in the predomain region (euANT2, euANT3, and euANT4). Our expression studies show that the euAP2 homologue from Amborella trichopoda, the putative sister to all other angiosperms, is expressed in all floral organs as well as leaves.

Motivation: The gene expression intensity information conveyed by (EST) Expressed Sequence Tag data can be used to infer important cDNA library properties, such as gene number and expression patterns. However, EST clustering errors, which often lead to greatly inflated estimates of obtained unique genes, have become a major obstacle in the analyses. The EST clustering error structure, the relationship between clustering error and clustering criteria, and possible error correction methods need to be systematically investigated., Results: We identify and quantify two types of EST clustering error, namely, Type I and II in EST clustering using CAP3 assembling program. A Type I error occurs when ESTs from the same gene do not form a cluster whereas a Type II error occurs when ESTs from distinct genes are falsely clustered together. While the Type II error rate is <1.5% for both 5' and 3' EST clustering, the Type I error in the 5' EST case is approximately 10 times higher than the 3' EST case (30% versus 3%). An over-stringent identity rule, e.g., P >/= 95%, may even inflate the Type I error in both cases. We demonstrate that approximately 80% of the Type I error is due to insufficient overlap among sibling ESTs (ISO error) in 5' EST clustering. A novel statistical approach is proposed to correct ISO error to provide more accurate estimates of the true gene cluster profile.

The possibility of performing reliable post-mortem analysis of carbohydrate-deficient transferrin (CDT) concentration in vitreous humour (VH) by using a commercial assay designed for serum analysis (CDTect(TM)) as well as the usefulness of VH-CDT as a marker of alcohol misuse and possible withdrawal-related death were evaluated in a forensic sample. Detectable VH-CDT was found in 20 of 21 alcoholic subjects and in two of seven controls. By using the detection limit of the CDTect(TM) method (VH-CDT = 5 U/l) as cut-off level for a positive test, the alcoholic group was significantly separated from the control group (P = 0.0024, Fisher's exact test). The sensitivity and specificity of the test was 95% and 71%, giving a positive and a negative predictive value of 91% and 83%, respectively. Time-dependent changes of VH-CDT in the dead body could not unequivocally be excluded, which must be considered when selecting cases suitable for VH-CDT analysis. We conclude that adding VH-CDT analysis to ordinary alcohol tests may become useful in forensic medicine for establishing the so-called 'alcoholic state', which may provide a tool in research dealing with the relation between alcohol withdrawal and various causes of death in alcoholics.

To investigate the cause and effect relationship between hyperinsulinemia and the increased amounts of farnesylated p21Ras, we performed hyperinsulinemic euglycemic clamps in normal weight volunteers as well as in normal mice and dogs. Insulin infusions significantly raised the amounts of farnesylated p21Ras in the white blood cells of humans, in liver samples of mice and dogs, and in aorta samples of mice. Obese hyperinsulinemic individuals and dogs (made hyperinsulinemic by surgical diversion of the pancreatic outflow from the portal vein into the vena cava) displayed increased amounts of farnesylated p21Ras before the hyperinsulinemic clamps. Infusions of insulin did not alter the already increased levels of farnesylated p21Ras in these experimental models. To further investigate the role of acquired insulin resistance in modulating insulin's effect on p21Ras prenylation, we induced insulin resistance in rats by glucosamine infusion. Insulin-resistant glucosamine-treated animals displayed significantly increased farnesylated p21Ras in response to insulin infusion compared to that in control saline-treated animals. Transgenic models of insulin resistance (heterozygous insulin receptor substrate-1 knockout mice, A-ZIP/F-1 fatless mice, and animals overexpressing glutamine:fructose-6-phosphate amidotransferase) contained increased amounts of farnesylated p21Ras. We conclude that hyperinsulinemia, either endogenous (a prominent feature of insulin resistance) or produced by infusions of insulin, increases the amounts of farnesylated p21Ras in humans, mice, and dogs. This aspect of insulin action may represent one facet of the molecular mechanism of the potentially detrimental influence of hyperinsulinemia.

Dexamethasone (DEX) has been shown to elicit growth stunting and cleft palate in rat fetuses. This investigation characterized DEX dosimetry as various pharmacokinetic parameters and evaluated their impact on developmental toxicity endpoints. DEX pharmacokinetics was evaluated as a single dose on either gestation day (GD) 9 or 14, as well as on GD 14 after multiple daily dosing from GD 9 to GD 14. An additional set of pregnant rats was dosed with DEX on GD 9 through GD 14, pharmacokinetic evaluation was conducted on GD 14 through GD 16, and teratological evaluation was conducted following sacrifice on GD 20. For all pharmacokinetic evaluations, a subcutaneous (sc) injection of 0.8 mg DEX/kg body weight together with 50 microCi 3H-DEX was administered to Sprague-Dawley rats. Blood, urine, and feces were collected for 24 or 48 h. At GD 20 sacrifice, maternal tissues as well as fetal brain and liver samples were collected as part of the laparotomy. All samples were assayed using scintillation spectrometry. DEX pharmacokinetic parameters remained similar whether dosing occurred early (GD 9) or late (GD 14) in organogenesis, or dosing occurred on multiple sequential days (GD 9-14). DEX produced maternal and fetal weight loss, fetal lethality, and cleft palate. DEX a-half-life was positively correlated with the percentage of implants affected [(number of non-live + number with cleft palate)/number of implants]/litter. Neither the area under the concentration-time curve (AUC), the maximum maternal plasma concentration (Cmax), nor the terminal phase beta-half-life correlated with any fetal outcome parameters. The correlation between the percentage of the litter that was affected and half-life was improved if AUC was added in a stepwise multiple regression. These data suggest that the length of time that DEX is present in the maternal plasma at a sufficiently high concentration (i.e., slower tissue distribution of DEX) appears to be important in determining the risk of an adverse outcome in the offspring.

Morphometric and physiological measurements in the parietal cortex of rats with 2-kidney-1-clip renal hypertension and their normotensive controls indicated a 23% increase in capillary bed volume accompanied by a 32% reduction in the rate of cortical blood flow in the renal hypertensive animals. From these measures, we estimated an 83% increase in the duration of blood transit through the cortical capillary network of renal hypertensive rats, a new expression of altered microvascular function in the brain of this hypertensive model. The rate of glucose utilization in the cerebral cortex of renal hypertensive animals was not different from that observed for normotensive animals. Thus, for capillary networks in cerebral cortex of renal hypertensive rats, we demonstrated markedly reduced rates of perfusion independent of tissue metabolic factors, despite expansion of capillary bed volume.