The Effect of Temperature Variability on Biological Responses of Ectothermic Animals-A Meta-Analysis.

Climate change is altering temperature means and variation, and both need to be considered in predictions underpinning conservation. However, there is no consensus in the literature regarding the effects of temperature fluctuations on biological functions. Fluctuations may affect biological responses because of inequalities from non-linear responses, endocrine regulation or exposure to damaging temperatures. Here we establish the current state of knowledge of how temperature fluctuations impact biological responses within individuals and populations compared to constant temperatures with the same mean. We conducted a meta-analysis of 143 studies on ectothermic animals (1492 effect sizes, 118 species). In this study, 89% of effect sizes were derived from diel cycles, but there were no significant differences between diel cycles and shorter (<8 h) or longer (>48 h) cycles in their effect on biological responses. We show that temperature fluctuations have little effect overall on trait mean and variance. Nonetheless, temperature fluctuations can be stressful: fluctuations increased 'gene expression' in aquatic animals, which was driven mainly by increased hsp70. Fluctuating temperatures also decreased longevity, and increased amplitudes had negative effects on population responses in aquatic organisms. We conclude that mean temperatures and extreme events such as heat waves are important to consider, but regular (particularly diel) temperature fluctuations are less so.

Impact of Baseline Renal Insufficiency on Piflufolastat F-18 Performance and Investigation of Changes in Renal Function Following Piflufolastat F-18 Administration: Results From the OSPREY Trial.

INTRODUCTION: Piflufolastat F-18, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, is predominantly eliminated via urinary excretion, and the kidneys have one of the highest absorbed doses. Therefore, this subgroup analysis aimed to investigate the impact of piflufolastat F-18 on renal function and its diagnostic performance in patients stratified by baseline renal function. PATIENTS AND METHODS: The OSPREY clinical trial enrolled 2 cohorts: A-high-risk patients undergoing radical prostatectomy with pelvic lymphadenectomy, and B-patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Baseline estimated glomerular filtration rates were calculated, and patients were stratified by baseline chronic kidney disease (CKD) stage. Changes in serum creatinine within 28 days postdose and diagnostic performance of piflufolastat F-18 were assessed for each CKD stage group in both cohorts. RESULTS: 385 patients (cohort A, n = 268; cohort B, n = 117) underwent piflufolastat F-18-PET/CT. Baseline and postpiflufolastat F-18 median creatinine levels (mg/dL) were similar for patients in cohort A (0.95 [n = 264] vs. 0.95 [n = 252], respectively) and cohort B (0.93 [n = 116] vs. 0.96 [n = 84], respectively). Among 332 men (cohort A, n = 249; cohort B, n = 83) with baseline and postpiflufolastat creatinine measurements, there were minimal changes in creatinine across all baseline CKD stage groups (median change ranged from -0.02 to 0.023 in groups with >1 patient). The diagnostic performance of piflufolastat F-18 showed no meaningful differences when stratified by baseline CKD stage. CONCLUSION: Piflufolastat F-18 appears to be safe and effective for imaging prostate cancer, including men with mild/moderate renal insufficiency.

Six of one, half a dozen of the other? Examining measurement properties of different potentially traumatic event polyvictimization operationalizations using a multiverse analysis framework.

Numerous differences exist between and within research projects related to assessment and operationalization of potentially traumatic events (PTEs) for youth, especially when measuring polyvictimization. However, few studies have systematically examined how polyvictimization measurement differences influence PTE's relation to functioning. This study sought to address these knowledge gaps by conducting a secondary data multiverse replication (SDMR) to systematically (re)evaluate PTE polyvictimization measurement approaches. Participants included 3297 adolescents (Mage = 14.63; 50.59% female; 65.15% white) from the National Survey of Adolescents-Replication study who completed a structured interview on PTE exposure and emotional and behavioral health (i.e., posttraumatic stress and major depressive disorder, drug and alcohol use, and delinquency). Results indicated that PTE operationalizations using a count variable tended to demonstrate better model performance and prediction of youth at-risk of emotional and behavioral health challenges, compared to models using a binary (yes/no) PTE operationalization. Differences in model performance and prediction were less distinct between models examining multiple forms of a single type of PTE (e.g., maltreatment, community violence), compared to models examining multiple PTE types. These findings emphasize the importance of using multidimensional approaches to PTE operationalization and the need for more multiverse analyses to improve PTE evidence-based assessment.

The genome sequence of the Common Alderfly, Sialis lutaria (Linnaeus, 1758).

We present a genome assembly from an individual Sialis lutaria (alderfly; Arthropoda; Insecta; Megaloptera; Sialidae). The genome sequence is 462.0 megabases in span. Most of the assembly is scaffolded into 15 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 15.59 kilobases in length.

Short QT intervals in African lions.

The cardiac conduction system in large carnivores, such as the African lion (Panthera leo), represents a significant knowledge gap in both veterinary science and in cardiac electrophysiology. Short QT intervals have been reported from zoo-kept, anaesthetized lions, and our goal was to record the first ECGs from wild, conscious lions roaming freely, and compare them to zoo-kept lions under the hypothesis that short QT is unique to zoo-kept lions. Macroscopic and histological examinations were performed on heart tissue removed from nine healthy zoo lions. ECGs were recorded from the nine anaesthetized zoo-kept lions, and from 15 anaesthetized and conscious wild lions in Africa. Our histological and topographical description of the lion's heart matched what has previously been published. In conscious lions, the ECG recordings revealed a mean heart rate of 70 ± 4 beats/min, with faster heart rates during the night. PQ and QT intervals were heart rate dependent in the conscious lions. Interestingly, QT intervals recorded in wild lions were markedly longer than QT intervals from zoo lions (398 ± 40 vs. 297 ± 9 ms, respectively; P < 0.0001). Anaesthesia or heart rate did not account for this difference. We provide a comprehensive description of the cardiac anatomy and electrophysiology of wild and zoo-kept lions. QT intervals were significantly shorter in zoo lions, suggesting functional disparities in cardiac electrophysiology between wild and zoo-kept lions, potentially related to physical fitness. These findings underscore the plasticity of cardiac electrophysiology and may be of value when reintroducing endangered species into the wild and when managing lions in human care.

Impact of tongue base mucosectomy on quality-of-life outcomes: systematic review and single-centre experience.

PURPOSE: Tongue base mucosectomy (TBM) is a well-established procedure in investigating cervical squamous cell carcinoma of occult primary. However, its risks have not been balanced against its benefits with validated tools. METHODS: A systematic literature review was conducted for reported complications and quality-of-life outcomes following TBM. The complications and quality-of-life outcomes following TBM at our institution are then reported using objective metrics and validated assessment tools, including Performance Status Scale for Head and Neck Cancer Patients (PSS-HNS), University of Washington Quality-of-life Questionnaire (UW-QOL) and M. D. Anderson Dysphagia Inventory (MDADI). RESULTS: Eighteen studies met the criteria for inclusion in the systematic review. Of these, 9 addressed swallowing outcomes described in text, without using validated assessment tools. No studies reported taste, speech and pain outcomes after TBM. Post-operative bleeding was not consistently reported. 20 patients underwent robotic TBM at our institution between 2017 and 2023. The primary tumour was identified in 50% (10/20) of cases. The median time to commencing soft diet and median time of NG feeding was 0 days. The median return to normalcy of diet score was 95. Median post-treatment UW-QOL pain and swallowing scores were 100 and 70 respectively. The median speech score was 100, saliva 70, and taste 70. The median normalised MDADI scores were: global 80; emotional 67; functional 80 and physical 65. CONCLUSIONS: Validated assessment tools better inform patients about treatment options and can help compare post-TBM results across institutions. Our data demonstrates that TBM patients have a functional post-operative swallow, are pain and gastrostomy free, even after adjuvant treatment. Routine post-operative insertion of NG tube is not necessary.

Drinking motives link positive and negative life events to problematic alcohol use during the COVID-19 pandemic: a longitudinal study.

PURPOSE: Stressful life events are associated with problematic drinking, and alcohol misuse has been exacerbated during the coronavirus disease 2019 (COVID-19) pandemic. While coping motives may account for this association, positive life events (PLEs) and enhancement motives are understudied. To address these gaps, we examined the associations of history of alcohol use disorder (AUD), negative life events (NLEs), and PLEs with problematic alcohol use and tested coping and enhancement motives as mediators. METHODS: The sample included baseline and follow-up data from 241 participants enrolled in the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol Study. Endorsements of past year PLEs and NLEs and their associations with problematic alcohol use were examined. Among the 202 current drinkers, path analyses tested mediational pathways via coping and enhancement motives. RESULTS: The top two PLEs were change in work conditions (21.6%) and taking a vacation (20.3%). The top two NLEs were change in social activities (36.5%) and major change in recreation (26.6%). Individuals with a history of AUD and those who experienced more NLEs reported higher coping and enhancement motives, which were associated with higher problematic alcohol use. Individuals who experienced more PLEs reported lower coping motives, which was associated with lower problematic alcohol use. CONCLUSIONS: Besides coping motives, enhancement motives were also associated with pandemic problematic alcohol use. Alcohol interventions targeting reward- and relief-driven drinking patterns may be beneficial to individuals with a history of AUD and those who experienced more NLEs. More research is needed to study PLEs which may help inform the development of strength-based alcohol interventions.

New Processes for Ionizing Nonvolatile Compounds in Mass Spectrometry: The Road of Discovery to Current State-of-the-Art.

This Perspective covers discovery and mechanistic aspects as well as initial applications of novel ionization processes for use in mass spectrometry that guided us in a series of subsequent discoveries, instrument developments, and commercialization. Vacuum matrix-assisted ionization on an intermediate pressure matrix-assisted laser desorption/ionization source without the use of a laser, high voltages, or any other added energy was simply unbelievable, at first. Individually and as a whole, the various discoveries and inventions started to paint, inter alia, an exciting new picture and outlook in mass spectrometry from which key developments grew that were at the time unimaginable, and continue to surprise us in its simplistic preeminence. We, and others, have demonstrated exceptional analytical utility. Our current research is focused on how best to understand, improve, and use these novel ionization processes through dedicated platforms and source developments. These ionization processes convert volatile and nonvolatile compounds from solid or liquid matrixes into gas-phase ions for analysis by mass spectrometry using, e.g., mass-selected fragmentation and ion mobility spectrometry to provide accurate, and sometimes improved, mass and drift time resolution. The combination of research and discoveries demonstrated multiple advantages of the new ionization processes and established the basis of the successes that lead to the Biemann Medal and this Perspective. How the new ionization processes relate to traditional ionization is also presented, as well as how these technologies can be utilized in tandem through instrument modification and implementation to increase coverage of complex materials through complementary strengths.

Expanding cyclodextrin use in normal phase and super/subcritical fluid chromatographic modes for the chiral separation of 1,4-dihydropyridines.

Cyclodextrin-based stationary phases are important chiral selectors in liquid chromatography. These chiral selectors are most commonly used in the reversed-phase mode because native cyclodextrin assumes a torus conformation with a hydrophobic cavity, facilitating inclusion complexation in aqueous environments. However, the value of native and aliphatic-derivatized cyclodextrins in other modes, such as the normal phase liquid chromatography (NPLC) or super/subcritical fluid chromatography (SFC), remains unexplored. In this work, we report chiral separations of pharmaceutically relevant compounds with the 1,4-dihydropyridine (DHP) scaffold on a 2-hydroxypropyl-ß-cyclodextrin (CD-RSP) stationary phase in NPLC and SFC modes. Although CD-RSP is conventionally considered only effective in the reversed-phase mode, we show that these compounds tend to separate better in other modes. This is particularly apparent for analytes with hydrogen-bonding moieties. We propose that the separation mechanism primarily depends on external adsorption rather than inclusion complexation. The negligible impact of a complexation-competitive additive on retention in non-aqueous modes further supports this claim. Additionally, van Deemter analysis demonstrated the efficiency and environmental benefit of using this stationary phase in the SFC mode, further highlighting the promise of aliphatic derivatized cyclodextrin stationary phases for greener separations.

Engineered Extracellular Vesicles for Combinatorial TNBC Therapy: SR-SIM-Guided Design Achieves Substantial Drug Dosage Reduction.

Triple negative breast cancer is an aggressive subtype of breast cancer that has no therapeutic targets, relies on chemotherapeutics for treatment, and is in dire need of novel therapeutic approaches for improved patient outcomes. Extracellular vesicles serve as intercellular communicators and have been proposed as ideal drug delivery vehicles. Here, extracellular vesicles were engineered with RNA nanotechnology to develop Triple negative breast cancer tumor inhibitors. Utilizing Super Resolved-Structured Illumination Microscopy, extracellular vesicles were optimized for precise Survivin siRNA conjugated to chemotherapeutics loading and CD44 aptamer ligand decoration, thereby enhancing specificity towards triple negative breast cancer cells. Conventional treatments typically employ chemotherapy drugs Gemcitabine and Paclitaxel at dosages on the order of mg/kg respectively, per injection (IV) in mice. In contrast, engineered extracellular vesicles encapsulating these drugs saw functional tumor growth inhibition at significantly reduced concentrations: 2.2 µg/kg for Gemcitabine or 5.6 µg/kg for Paclitaxel, in combination with 21.5 µg/kg Survivin-siRNA in mice. The result is a substantial decrease of chemotherapeutic dose required, by orders of magnitude, compared to standard regimens. In vivo and in vitro evaluations in a triple negative breast cancer orthotopic xenograft mouse model demonstrated the efficacy of this reduced dosage strategy, indicating potential for decreased chemotherapy-associated toxicity.

Where is the boundary of the human pseudoautosomal region?

A recent publication describing the assembly of the Y chromosomes of 43 males was remarkable not only for its ambitious technical scope but also for the startling suggestion that the boundary of the pseudoautosomal region 1 (PAR1), where the human X and Y chromosomes engage in crossing-over during male meiosis, lies 500 kb distal to its previously reported location. Where is the boundary of the human PAR1? We first review the evidence that mapped the PAR boundary, or PAB, before the human genome draft sequence was produced, then examine post-genomic datasets for evidence of crossing-over between the X and Y, and lastly re-examine contiguous sequence assemblies of the PAR-NPY boundary to see whether they support a more distal PAB. We find ample evidence of X-Y crossovers throughout the 500 kb in question, some as close as 246 bp to the previously reported PAB. Our new analyses, combined with previous studies over the past 40 years, provide overwhelming evidence to support the original position and narrow the probable location of the PAB to a 201-bp window.

Neuropsychiatric Symptoms Cluster and Fluctuate Over Time in Behavioral Variant Frontotemporal Dementia.

Objectives: Cognitive and behavioral phenomena define behavioral variant frontotemporal dementia (bvFTD), but neuropsychiatric symptoms (NPS) outside the core criteria are common throughout the illness. Identifying how NPS cluster in bvFTD may clarify the underlying neurobiology of bvFTD-related NPS and guide development of therapies. Methodology: Participants (N=354) with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration Consortium. Dementia stage was defined as early (CDR® plus NACC FTLD ≤ 1) or advanced (CDR® plus NACC FTLD ≥ 1). Baseline and annual follow-up visit data were analyzed to compare NPS across stages of bvFTD. Psychiatric states were captured using the Neuropsychiatric Inventory-Questionnaire and Clinician Judgement of Symptoms. Polychoric cluster analysis was used to describe NPS clusters. Results: NPS were highly prevalent (≥ 90%) in early and late bvFTD. Four NPS clusters were identified based on magnitude of factor loadings: affective, disinhibited, compulsive, and psychosis. Neuropsychiatric symptoms fluctuated across visits. In the affective cluster, depression and anxiety showed the least visit-to-visit stability. In the disinhibited cluster, elation showed the least stability. Symptoms in the psychosis and compulsive clusters (hallucinations, delusions, obsessions/compulsions, and hyperorality) were largely stable, persisting from visit-to-visit in more than 50% of cases. Conclusion: NPS in bvFTD are frequent and cluster into four discrete groups in bvFTD. These clusters may result from specific neural network disruptions that could serve as targets for future interventions. The fluctuating nature of NPS in bvFTD suggests that they are not reliable markers of disease progression or stage.

Copper binding alters the core structure of amyloid fibrils formed by Y145Stop human prion protein.

Transmissible spongiform encephalopathies (or prion diseases) such as Creutzfeldt-Jacob disease, mad cow disease, and scrapie are characterized by accumulation in the brain of misfolded prion protein aggregates (PrPSc) that have properties of amyloid fibrils. Given that transition metal ions, such as copper and zinc, appear to be important for physiological functions of cellular PrP (PrPC) as well as for prion disease pathogenesis, exploring their role in the protein aggregation process is of considerable interest. Copper(II) in particular is well-known to bind to the four tandem octapeptide repeats (PHGGGWGQ) located in the N-terminal region of PrP (human PrP amino acids 60-91), as well as to additional histidine binding sites outside the octarepeat region with distinct binding modes depending on Cu2+ concentration. Here, using the Y145Stop human prion protein variant (huPrP23-144) as a model and a combination of multidimensional solution and solid-state NMR spectroscopy, atomic force microscopy and thioflavin T fluorescence assays we probed the binding of Cu2+ to monomeric huPrP23-144 and the impact of this binding on fibril assembly kinetics and their structural properties. Remarkably, we found that fibrils formed by huPrP23-144 containing one molar equivalent of bound Cu2+ adopt a core structure that is distinct from that found for huPrP23-144 in the absence of Cu2+ but, instead, corresponds to a conformational strain formed by huPrP23-144 containing the A117V mutation. A similar huPrP23-144 A117V-like amyloid core structure was adopted by a Cu2+-bound Δ51-91 huPrP23-144 deletion variant lacking the entire octarepeat region, suggesting that Cu2+ binding to His residues 96, 111 and 140 located near the C-terminus of huPrP23-144 is primarily responsible for the observed change in fibril conformation, potentially due to partial structuring of the intrinsically disordered huPrP23-144 by the bound Cu2+ during the fibril assembly process. We also found that fibrils formed by Cu2+-bound huPrP23-144 adopt the native huPrP23-144-like rather than A117V-like structure when the fibrillization reaction is seeded with pre-formed huPrP23-144 amyloid.

Genetic analysis of selection bias in a natural experiment: Investigating in-utero famine effects on elevated body mass index in the Dutch Hunger Winter Families Study.

Natural-experiment designs that compare survivors of in-utero famine exposure to unaffected controls suggest that in-utero undernutrition predisposes to development of obesity. However, birth rates drop dramatically during famines. Selection bias could arise if factors that contribute to obesity also protect fertility and/or fetal survival under famine conditions. We investigated this hypothesis using genetic analysis of a famine-exposed birth cohort. We genotyped participants in the Dutch Hunger Winter Families Study (DHWFS, N=950; 45% male), of whom 51% were exposed to the 1944-1945 Dutch Famine during gestation and 49% were their unexposed same-sex siblings or "time controls" born before or after the famine in the same hospitals. We computed body-mass index (BMI) polygenic indices (PGIs) in DHWFS participants and compared BMI PGIs between famine-exposed and control groups. Participants with higher polygenic risk had higher BMIs (Pearson r=0.42, p<0.001). However, differences between BMI PGIs of famine-exposed participants and controls were small and not statistically different from zero across specifications (Cohen's d=0.10, p>0.092). Our findings did not indicate selection bias, supporting the validity of the natural-experiment design within DHWFS. In summary, our study outlines a novel approach to explore the presence of selection bias in famine and other natural experiment studies.

Introducing macrocyclic glycopeptide columns as unique achiral stationary phases: Insights from hydrophobic subtraction model and in-silico modeling.

BACKGROUND: The need for stationary phases with unique selectivity in reversed-phase liquid chromatography has been of utmost importance to chromatographers for advancing the analysis of complex samples. Macrocyclic glycopeptide based stationary phases have been widely used for chiral separations with different chromatographic modes such as normal phase, reversed phase, and supercritical fluid chromatography. Given the multimodal retention mechanisms namely π-π complex interaction, hydrogen bonding, dipole-dipole interaction, and strong Coulombic interactions by which analytes are separated using the macrocyclic glycopeptides, these stationary phases are expected to provide novel selectivity when used under the reversed phase for achiral separations. RESULTS: Herein, for the first time we have conducted a systematic study using the improved hydrophobic subtraction model (HSM) which incoporates dipole-dipole interactions to demonstrate the novel selectivity offered by four different macrocyclic glycopeptide based stationary phases, namely NicoShell, TeicoShell, TagShell, and VancoShell. A comparison of the HSM parameters for these columns has been made with 551 commercially available reversed phase stationary phases and the differences in the values point to the importance of adding these columns to the already existing arsenal. These stationary phases offer separations over a wide range of pH and show variability in selectivity depending on the pH of the mobile phase which make them versatile for method development in the reversed phase mode. Additionally, we have provided an actual example of a separation from an Amgen discovery project using the VancoShell column aided by computer-assisted modelling. SIGNIFICANCE: This is the first report characterizing macrocyclic glycopeptides for achiral RPLC applications. The selectivity of these stationary phases were found to be unique when compared to other commercially available stationary phases thereby acting as their own class of columns. The unusual selectivity of the columns enabled separation of complex pharmaceutical samples.

Observation of metastable structures of the ethylene glycol-water dimer in helium nanodroplets.

Ethylene glycol (EG) is the simplest organic diol. Here we measure infrared spectra of the EG monomer and its dimer with water, the complex, EG(H2O), embedded in superfluid helium nanodroplets. For the monomer, only a single, gauche, conformation is observed. For EG(H2O), no trace of the global energy minimum is seen, a structure that would maximize the hydrogen bonding contacts. Instead, only metastable structures are formed, suggesting that dimerization in a superfluid environment leads to kinetic trapping in local energy minima. In addition, we obtain evidence for a dimer where the conformation of EG switches from gauche to trans on account of dimerization with a water molecule. This observation is assumed to be driven over an energy barrier by utilizing the energy released as hydrogen bonding occurs.

Tumor NOS2 and COX2 Spatial Juxtaposition with CD8+ T Cells Promote Metastatic and Cancer Stem Cell Niches that Lead to Poor Outcome in ER- Breast Cancer.

Estrogen receptor-negative breast cancer is an aggressive subtype with limited therapeutic options. Elevated nitric oxide synthase (NOS2) and cyclo-oxygenase (COX2) mediates immunosuppression and poor survival in these tumors. Therefore, the influence of tumor NOS2/COX2 on immune architecture was examined in 16 African American and 5 Caucasian ER- tumors. Elevated tumor NOS2/COX2 limited CD8+ T cell infiltration at 5-yr survival. Distinct CD8+/-NOS2+/-COX2+/- phenotypes defining metastatic and cancer stem cell niches, and immune desert regions were identified. These results were supported by an unbiased, unsupervised nonlinear dimensionality-reduction UMAP technique incorporating spatial relations between cells and validated in a separate gene expression cohort using NOS2/CD8 and COX2/CD8 ratios. Additionally, elongated tumor cells were specifically in CD8-NOS2+COX2+ regions, suggesting metastatic hot spots. This work demonstrates predictive power of spatial analyses of CD8/NOS2/COX2 architecture and supports the use of clinically available NOS2/COX2 inhibitors for improved survival in patients with these aggressive tumors.

Observation and enhancement through alkali metal doping of p-type conductivity in the layered oxyselenides Sr2ZnO2Cu2Se2 and Ba2Zn1-x O2-x Cu2Se2.

The optoelectronic properties of two layered copper oxyselenide compounds, with nominal composition Sr2ZnO2Cu2Se2 and Ba2ZnO2Cu2Se2, have been investigated to determine their suitability as p-type conductors. The structure, band gaps and electrical conductivity of pristine and alkali-metal-doped samples have been determined. We find that the strontium-containing compound, Sr2ZnO2Cu2Se2, adopts the expected tetragonal Sr 2 Mn 3 SbO 2 structure with I4/mmm symmetry, and has a band gap of 2.16 eV, and a room temperature conductivity of 4.8 × 10-1 S cm-1. The conductivity of the compound could be increased to 4.2 S cm-1 when sodium doped to a nominal composition of Na0.1Sr1.9ZnO2Cu2Se2. In contrast, the barium containing material was found to have a small zinc oxide deficiency, with a sample dependent compositional range of Ba2Zn1-x O2-x Cu2Se2 where 0.01 < x < 0.06, as determined by single crystal X-ray diffraction and powder neutron diffraction. The barium-containing structure could also be modelled using the tetragonal I4/mmm structure, but significant elongation of the oxygen displacement ellipsoid along the Zn-O bonds in the average structure was observed. This indicated that the oxide ion position was better modelled as a disordered split site with a displacement to change the local zinc coordination from square planar to linear. Electron diffraction data confirmed that the oxide site in Ba2Zn1-x O2-x Cu2Se2 does not adopt a long range ordered arrangement, but also that the idealised I4/mmm structure with an unsplit oxide site was not consistent with the extra reflections observed in the electron diffractograms. The band gap and conductivity of Ba2Zn1-x O2-x Cu2Se2 were determined to be 2.22 eV and 2.0 × 10-3 S cm-1 respectively. The conductivity could be increased to 1.5 × 10-1 S cm-1 with potassium doping in K0.1Ba1.9Zn1-x O2-x Cu2Se2. Hall measurements confirmed that both materials were p-type conductors with holes as the dominant charge carriers.

Acute freshwater CO2 exposure does not impair seawater transfer in three different sizes of Atlantic salmon (Salmo salar) subjected to different photoperiod manipulations.

There is a growing interest in Atlantic salmon (Salmo salar) aquaculture to extend the time fish are reared in freshwater (FW) recirculating aquaculture systems (RAS), producing larger FW salmon that can then be induced to undergo smoltification before transfer into marine net pens for grow-out and harvest. Smolts can be produced by photoperiod (PT) manipulation in RASs, but little is known about how delaying smoltification to larger body sizes affects susceptibility to elevated CO2 levels (hypercapnia), which can occur at high stocking densities in FW RAS or during transport from FW RAS rearing facilities to marine net pens. To address this, Atlantic salmon were reared from hatch to one of three different sizes (~230, ~580, or ~1300 g) in FW (3 ppt) under continuous light (24:0, light:dark). Once fish reached the desired sizes, a group of salmon were maintained on continuous light 24L:0D to serve as a control salmon. A second group of salmon were exposed to 8 weeks of 12L:12D and then to 4 weeks of 24L:0D to serve as PT treatment salmon, which is the PT manipulation commonly used in Atlantic salmon aquaculture to induce smoltification. At the end of PT manipulation, both control and PT treatment salmon were exposed to 0% or 1.5% CO2 (30 mg/L) for 96 h in FW and then transferred to air-equilibrated seawater (SW, 35 ppt, normocapnia). Salmon were sampled at the end of the 96-h FW CO2 exposure and at 24 h and 7 days in SW for measurements of blood ion/acid-base status, muscle water content (MWC), and gill and kidney Na+/K+ ATPase (NKA) activity. Exposure to 96 h of CO2 in FW resulted in acid-base disturbances in fish from all three size classes, with decreases in blood pH and increases in blood PCO2 and plasma [HCO3 -] but no mortality. Despite these large acid-base disturbances in FW, after transfer to normocapnic SW, there were no significant effects of CO2 exposure on extracellular blood pH, intracellular red blood cell pH, or plasma osmoregulatory status for all three sizes of post-smolt salmon. In general, SW transfer was associated with significant increases in plasma ions and osmolality, as well as gill and kidney NKA activity after 24 h and 1 week in SW with no significant impacts between different sizes of salmon. Thus, exposure to 30 mg CO2/L that mimics levels experienced during transport from FW RAS to an SW transfer site may have minimal effects on Atlantic salmon smolts up to 1300 g.

Characterization of neurologic disease-associated Streptococcus suis strains within the United States swine herd and use of diagnostic tools.

Streptococcus suis negatively impacts swine health, posing diagnostic and preventative challenges. S. suis can induce disease and also quietly reside on mucosal surfaces. The limited use of diagnostic tools to identify disease-associated strains and rule out differential diagnoses, alongside the complex ecology of S. suis, poses significant challenges in comprehending this important pathogen and defining pathotypes. This study evaluated 2,379 S. suis central nervous system (CNS) isolates from diagnostic submissions between 2015 and 2019. Isolates originating from submissions with histologic evidence of CNS infection (n = 1,032) were further characterized by standard and advanced diagnostic techniques. We identified 29 S. suis serotypes and 4 reclassified serotypes as putative causes of CNS disease. Among these, serotypes 1 and 7 emerged as the predominant putative causes of CNS infection (32% of submissions). Furthermore, 51 sequence types (STs), of which 15 were novel, were detected with ST1 predominating. Through whole-genome sequencing of 145 isolates, we observed that five commonly used virulence-associated genes (VAGs; epf, mrp, sly, ofs, and srtF) were not present in most disease-associated isolates, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) yielded false-positive results in 7% of isolates. These data indicate that (i) clinical signs and site of isolation alone are insufficient for defining a pathotype, (ii) S. suis serotypes and STs associated with CNS infection are more diverse than previously reported, (iii) MALDI-TOF MS may need to be supplemented with additional diagnostic tools for precise S. suis identification, and (iv) VAGs remain an unreliable means for identifying isolates associated with CNS disease.IMPORTANCEStreptococcus suis is an important and complex systemic bacterial pathogen of swine. Characterization of S. suis strains originating from pigs with histologic confirmation of neurologic disease is limited. Review of swine diagnostic submissions revealed that fewer than half of cases from which S. suis was isolated from the brain had histologic evidence of neurologic disease. This finding demonstrates that clinical signs and site of isolation alone are not sufficient for identifying a neurologic disease-associated strain. Characterization of strains originating from cases with evidence of disease using classic and advanced diagnostic techniques revealed that neurologic disease-associated strains are diverse and commonly lack genes previously associated with virulence.