Abstract Background Biliary tract cancers (BTCs) include intrahepatic (IHC), hilar, distal bile duct (DBD) and gallbladder carcinoma (GBC). Neutrophil/lymphocyte ratio (NLR), a marker of host ...inflammation, is prognostic in several cancers but has not been reviewed in large BTC series, or advanced BTC (ABTC) at diagnosis. Patients and methods Baseline demographics and NLR at diagnosis were retrospectively evaluated in 864 consecutive patients with BTC treated from January 1987 to December 2012. The association between NLR and overall survival (OS) was determined using a multivariable Cox proportional hazards model. Results Eight hundred and sixty-four patients were included in the analysis, of which 62% had ABTC and 38% had surgery with curative intent. Median age was 65 years, 444 (51%) were male and 727 (84%) had performance status (PS) ⩽2. A NLR ⩾3.0, PS >2, IHC primary, stage, lack of surgery, haemoglobin <110 g/L and albumin <40 g/L were associated with significantly worse OS on multivariable analysis. A NLR ⩾3.0 was an independent prognostic factor for OS for the entire cohort; median OS was 21.6 months versus 12.0 months for patients with NLR <3.0 versus NLR ⩾3.0 respectively (adjusted hazard ratio (HR)-1.26, 95% confidence interval (CI); 1.06–1.50, P = 0.01). NLR was also prognostic in patients with ABTC (HR-1.26, 95% CI; 1.02–1.56, P = 0.035) and hilar cancer: overall group ( N = 149) (HR-1.70, 95% CI; 1.10–2.50, P = 0.01) and advanced group ( N = 111) (HR-1.57, 95% CI; 1.04–2.44, P = 0.048). Conclusion Baseline NLR is a readily available and inexpensive prognostic biomarker in patients with BTC and likely warrants validation in large prospective clinical trials.
When selecting a nest site, mallards (Anas platyrhynchos) balance differing habitat requirements for the nesting and brood‐rearing periods, such that the juxtaposition of these habitats in the ...landscape may influence the female's reproductive strategy and reproductive success. Mallard populations in the northeastern United States have declined since the mid‐1990s, and increasing urban development in this region may pose risks to broods and cause high duckling mortality. We assessed mallard brood and duckling survival in the urbanized landscapes of Connecticut, USA, and evaluated whether differences in brood movements, home ranges, and habitat use in urbanized areas influence brood survival. We monitored 32 mallard broods from females with global positioning system (GPS) transmitters in Connecticut in 2021 and 2022. Apparent brood survival to 30 days (0.48, n = 29 broods) was comparable to previous estimates in the Northeast (range = 0.21–0.72), but individual duckling survival (0.18, n = 257 ducklings) was lower than many previous estimates for this region (range = 0.14–0.44), suggesting this parameter warrants continued evaluation because it may be contributing to population declines in Connecticut and the greater Northeast region. Mallard females demonstrated different reproductive strategies and seemed to prioritize either high‐quality nesting habitat or proximity to high‐quality brood‐rearing habitat. High‐quality nesting habitat is not necessarily near high‐quality brood‐rearing habitat, and 61% (17/28) of females moved their ducklings an average of 1.1 ± 0.9 km (SD) shortly after hatch to a brood‐rearing site, often traveling along small streams. A similar proportion of successful (9/12) and failed (7/13) broods moved. We provide evidence of limited availability of brood‐rearing habitat, as females moved long distances to brood‐rearing wetlands and only 1 brood made additional inter‐wetland moves. Management actions that create or modify nesting and brood‐rearing habitat should consider connectivity between these sites; females may choose to nest away from wetlands to minimize exposure to predators but may depend on small streams for travel to brood‐rearing wetlands.
In the urbanized landscapes of Connecticut, mallard brood survival was comparable to previous estimates in the Northeast, but duckling survival was lower than previously reported, suggesting this parameter warrants continued evaluation as it may be contributing to population declines in Connecticut and the greater Northeast region. Mallard females demonstrated different reproductive strategies, prioritizing either high‐quality nesting or brood‐rearing habitat. Half of females moved their broods an average of 1.1 ± 0.9 km after hatch, often traveling along small streams, suggesting that management actions should consider the connectivity of nesting and brood‐rearing habitat for mallards.
Aims
The purpose of this study was to investigate the regulatory mechanism of ε‐PL on Shewanella putrefaciens.
Methods and Results
Proteomics analysis of inhibitory effect of ε‐PL against S. ...putrefaciens was performed by label‐free quantitative assay based on high‐resolution mass spectrometry (MS). Quantification of 2206 proteins was obtained with high confidence, and a total of 36 differentially expressed proteins (DEPs), with 10 and 26 proteins showing upregulation and downregulation, respectively, were identified. Upon Go functional enrichment, 11, 5 and 8 specific Go terms in biological processes, molecular functions and cellular components were identified, respectively. Six KEGG pathways, including ‘ribosome’, were significantly enriched. Among the ribosome pathway, there were seven DEPs and all of them were distributed on large and small subunits of ribosome.
Conclusions
The significant downregulation of proteins, large subunits of ribosomal proteins RP‐L18, L30 and L27, small subunits ribosomal proteins S16 and S20, and RNA polymerase β' subunit protein rpoC were the critical action sites of ε‐PL to inhibit S. putrefaciens growth.
Significance and Impact of the Study
Shewanella putrefaciens is one of the representative fish‐spoilage bacteria regardless of fish type, and poses significant problems for the fish brewery. A better understanding of the antibacterial mechanism of ε‐PL on S. putrefaciens could make important contributions to development of biological control strategies of these economically important pathogens.
The melanocortin-3 receptor (MC3R) is a G protein–coupled receptor and potentially important in production traits. Three naturally occurring mutations (M54L, G104S, and L151R) in chicken MC3R (cMC3R) ...were reported previously to be associated with production traits. Here, we inserted the full-length cMC3R coding sequence into pcDNA3.1(+) and generated the 3 mutations by site-directed mutagenesis. The total and cell surface expression of the receptors was measured by flow cytometry. We analyzed the pharmacological characteristics, including binding and cyclic adenosine monophosphate (cAMP) and mitogen-activated protein kinase (MAPK) signaling, using 6 ligands (Nle4, D-Phe7-α-melanocyte stimulating hormone (MSH), α-, β-, γ-, and D-Trp8-γ-MSHs, and agouti-related peptide). All mutants had similar total and cell surface expression as the wild-type (WT) cMC3R. M54L had similar pharmacological properties as the WT cMC3R. G104S did not exhibit any specific binding but had minimal response to α-, β-, γ-, and D-Trp8-γ-MSH, although it generated 24% WT response when stimulated by NDP-MSH. Although L151R had normal binding, the responses to agonists were reduced to approximately 25% of that of the WT. In MAPK signaling, all 3 mutants showed significantly increased agonist-stimulated phosphorylation of extracellular signal-regulated protein kinases 1/2, indicating the existence of biased signaling at G104S and L151R. In summary, our studies demonstrated that although all 3 mutations are significantly associated with production traits, only G104S and L151R had severe defects in receptor pharmacology. How M54L might cause production trait differences remains to be investigated.
•Chicken MC3R mutants were shown to have defects in either binding (G104S) or signaling (L151R).•Some chicken MC3R mutants were shown to be biased receptors.•M54L had normal function, explaining its lack of association with production traits.•G104S and L151R were associated with variations in function that might impact production traits.
In this case series of four paediatric patients, we present the first described cases of immunotherapy‐responsive autoimmune nodopathy with IgG2 antineurofascin antibodies. In three cases, the ...antineurofascin antibodies were predominantly of the IgG2 subclass, a novel finding in comparison to previously described adult cases where IgG4 and/or IgG1/3 have typically been described. One patient had low signal for IgG2 with predominant IgG1 and IgG4 antibodies, a pattern commonly seen in adult patients. Two patients had antibodies targeting all three neurofascin isoforms (155, 186, and 140), whereas antibodies in the sera from the third targeted only the nodal isoforms 186 and 140, and the fourth patient only neurofascin 155. The three patients with IgG2 predominant antibodies appear to be responsive to intravenous immunoglobulin (IVIG) to varying degrees thus far, whereas the patient with IgG1/4 antibodies had poor response to IVIG but good response to steroids. Although the full clinical significance of IgG2 predominant antineurofascin antibodies in the context of childhood polyneuropathy remains unclear, emerging evidence of serological‐phenotypic correlation may inform prognostication and therapeutic decision‐making, warranting further study into this area.
What this paper adds
Paediatric immunotherapy‐responsive nodopathies were associated with antineurofascin antibodies predominantly of the IgG2 subclass in 3 out of 4 patients.
Identification of antibodies and understanding their phenotypic relevance could predict response to treatment and guide therapeutic decision‐making in children.
What this paper adds
Paediatric immunotherapy‐responsive nodopathies were associated with antineurofascin antibodies predominantly of the IgG2 subclass in 3 out of 4 patients.
Identification of antibodies and understanding their phenotypic relevance could predict response to treatment and guide therapeutic decision‐making in children.
Nanofluids are suspensions of nanoparticles into convectional heat transfer fluid to enhance the thermal conductivity of its base fluid. The roles of Brownian motion of nanoparticles and induced ...micro-convection in base fluid in enhancing the thermal conductivity of nanofluids were investigated using molecular dynamic (MD) simulation. The roles were determined by studying the effect of particle size on thermal conductivity and diffusion coefficient. Results show that the Brownian motion and induced micro-convection have insignificant effects on enhancing the thermal conductivity. The hydrodynamic effect is restricted by an amorphous-like interfacial fluid structure in the vicinity of the nanoparticle due to its higher specific area.
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