Characteristic Shift Research Articles

High-Rate Nitrite Production by Stable Denitrification Granular Sludge in a Reinforced-Mixing Up-Flow System: Shift in Spatiotemporal Characteristics of Functional Bacteria and Metagenomic Mechanisms

High-Rate Nitrite Production by Stable Denitrification Granular Sludge in a Reinforced-Mixing Up-Flow System: Shift in Spatiotemporal Characteristics of Functional Bacteria and Metagenomic Mechanisms

Exploration of the Photoluminescence Behavior and Emission Mechanism of Thioester Polyacrylamide Tablets During the Gradual Increase of Molecular Weight.

To enhance the photoluminescence (PL) of unconventional luminescent compounds, particularly their persistent room temperature phosphorescence (p-RTP) performance, compressing the powder into tablets has been demonstrated as a viable approach. Nevertheless, the alterations in the emission capability of PL in compacted tablets have not been comprehensively investigated. In this study, four polyacrylamide (PAM) with controllable molecular weight (MW) are fabricated from powder to tablets, and their PL emission properties are thoroughly examined and compared with corresponding powders to elucidate the emission mechanism. As MW increases, both PL and p-RTP emissions of the tablets gradually intensify, exhibiting significant enhancement compared to the corresponding powder while retaining the characteristic blue shift. Through small angle X-ray scattering (SAXS), construction of molecular models for tablets, detailed analysis of molecular interactions, and theoretical calculations are conducted to reasonably explain these emission phenomena using clustering-triggered emission (CTE) and average packing density promoted emission (PDE) mechanisms. These findings not only advance the understanding of nonconventional luminogens' emission mechanisms but also offer new insights for preparing nonconventional luminescent polymers with controllable p-RTP emission performance.

Arctic climate response to European radiative forcing: a deep learning study on circulation pattern changes

Abstract. Heterogeneous radiative forcing in mid-latitudes, such as that exerted by aerosols, has been found to affect the Arctic climate, though the mechanisms remain debated. In this study, we leverage deep learning (DL) techniques to explore the complex response of the Arctic climate system to local radiative forcing over Europe. We conducted sensitivity experiments using the Max Planck Institute Earth System Model (MPI-ESM1.2) coupled with atmosphere–ocean–land-surface components. Large-scale circulation patterns can mediate the impact of the forcing on Arctic climate dynamics. We employed a DL-based clustering approach to classify large-scale atmospheric circulation patterns. To enhance the analysis of how these patterns impact the Arctic climate, the poleward moist static energy transport (PMSET) associated with the atmospheric circulation patterns was incorporated as an additional similarity metric in the clustering process. Furthermore, we developed a novel method to analyze the circulation patterns' contributions to various climatic parameter anomalies. Our findings indicate that the negative radiative forcing over Europe alters existing circulation patterns and their occurrence frequency without introducing new ones. Specifically, our analysis revealed that while the regional radiative forcing alters the occurrence frequencies of the circulation patterns, these changes are not the primary drivers of the forcing's impact on the Arctic parameters. Instead, it is the shifts in the mean spatial characteristics of the atmospheric circulation patterns, induced by the forcing, that predominantly determine the effects on the Arctic climate. Our methodology facilitates the uncovering of complex, nonlinear interactions within the climate system, capturing nuances that are often obscured in broader seasonal anomaly analyses. This approach enables a deeper understanding of the dynamics driving observed climatic anomalies and their links to specific atmospheric circulation patterns.

Shift in Demographic Involvement and Clinical Characteristics of COVID-19 From Wild-Type SARS-CoV-2 to the Delta Variant in the Indian Population: In Silico Analysis.

The Delta variant (B.1.617.2) was considered the most dangerous SARS-CoV-2 strain; however, in-depth studies on its impact based on demographic and clinical characteristics of COVID-19 are scarce. We aimed to investigate the shift in demographic and clinical characteristics of the COVID-19 pandemic with the emergence of the SARS-CoV-2 Delta variant compared with the wild-type (WT) strain (B.1). A cross-sectional study of COVID-19 cases in the Indian population caused by the WT strain (B.1) and Delta variant of SARS-CoV-2 was performed. The viral genomic sequence metadata containing demographic, vaccination, and patient status details (N=9500, NDelta=6238, NWT=3262) were statistically analyzed. With the Delta variant, in comparison with the WT strain, a higher proportion of young individuals (<20 years) were infected (0-9 years: Delta: 281/6238, 4.5% vs B.1: 75/3262, 2.3%; 10-19 years: Delta: 562/6238, 9% vs B.1: 229/3262, 7%; P<.001). The proportion of women contracting infection increased (Delta: 2557/6238, 41% vs B.1: 1174/3262, 36%; P<.001). However, it decreased for men (Delta: 3681/6238, 59% vs B.1: 2088/3262, 64%; P<.001). An increased proportion of the young population developed symptomatic illness and were hospitalized (Delta: 27/262, 10.3% vs B.1: 5/130, 3.8%; P=.02). Moreover, an increased proportion of the women (albeit not men) from the young (Delta: 37/262, 14.1% vs B.1: 4/130, 3.1%; P<.001) and adult (Delta: 197/262, 75.2% vs B.1: 72/130, 55.4%; P<.001) groups developed symptomatic illness and were hospitalized. The mean age of men and women who contracted infection (Delta: men=37.9, SD 17.2 years; women=36.6, SD 17.6 years; P<.001; B.1: men=39.6, SD 16.9 years; women=40.1, SD 17.4 years; P<.001) as well as developing symptoms or being hospitalized (Delta: men=39.6, SD 17.4 years; women=35.6, SD 16.9 years, P<.001; B.1: men=47, SD 18 years; women=49.5, SD 20.9 years, P<.001) were considerably lower with the Delta variant than the B.1 strain. The total mortality was about 1.8 times higher with the Delta variant than with the WT strain. With the Delta variant, compared with B.1, mortality decreased for men (Delta: 58/85, 68% vs B.1: 15/20, 75%; P<.001); in contrast, it increased for women (Delta: 27/85, 32% vs B.1: 5/20, 25%; P<.001). The odds of death increased with age, irrespective of sex (odds ratio 3.034, 95% CI 1.7-5.2, P<.001). Frequent postvaccination infections (24/6238) occurred with the Delta variant following complete doses. The increased involvement of young people and women, the lower mean age for illness, higher mortality, and frequent postvaccination infections were significant epidemiological concerns with the Delta variant.

Inactivation induced by pathogenic Cav1.3 L-type Ca2+-channel variants enhances sensitivity for dihydropyridine Ca2+ channel blockers.

Pathogenic gain-of-function mutations in Cav1.3 L-type voltage-gated Ca2+-channels (CACNA1D) cause neurodevelopmental disorders with or without endocrine symptoms. We aimed to confirm a pathogenic gain-of function phenotype of CACNA1D de novo missense mutations A749T and L271H, and investigated the molecular mechanism causing their enhanced sensitivity for the Ca2+-channel blocker isradipine, a potential therapeutic for affected patients. Wildtype and mutant channels were expressed in tsA-201 cells and their gating analysed using whole-cell and single-channel patch-clamp recordings. The voltage-dependence of isradipine action was quantified using protocols inducing variable fractions of inactivated channels. The molecular basis for altered channel gating in the mutants was investigated using in silico modelling and molecular dynamics simulations. Both mutations were confirmed pathogenic due to characteristic shifts of voltage-dependent activation and inactivation towards negative potentials (~20 mV). At negative holding potentials both mutations showed significantly higher isradipine sensitivity compared to wildtype. The affinity for wildtype and mutant channels increased with channel inactivation as predicted by the modulated receptor hypothesis (30- to 40-fold). The IC50 was indistinguishable for wildtype and mutants when >50% of channels were inactivated. Mutations A749T and L271H induce pathogenic gating changes. Like wildtype, isradipine inhibition is strongly voltage-dependent. Our data explains their apparent higher drug sensitivity at a given negative voltage by the availability of more inactivated channels due to their more negative inactivation voltage range. Low nanomolar isradipine concentrations will only inhibit Cav1.3 channels in neurons during prolonged depolarized states without selectivity for mutant channels.

Serotypic and genotypic profile of dengue virus outbreaks in India between 2011 and 2017.

The epidemiology of dengue has been demonstrating significant changes in recent years, with rising incidence of infection in countries with known endemicity and occurrence of fresh outbreaks in previously unaffected territories. India, which has been a traditional hotspot dengue virus (DENV) transmission in the endemic south-east Asian region, has also been affected by the sweeping changes in dengue epidemiology. Two remarkable developments characterize the alterations witnessed by India 2011-2017. Firstly, all parts of the country have witnessed abrupt replacement of existing DENV lineages with emerging novel strains. Secondly, co-circulation of multiple serotypes of DENV have been reported from all across the country 2011-2017; thereby hinting at the transition of the country towards hyper-endemicity. Considering the potential clinical implications of such epidemiological transformation in terms increasing involvement of pediatric patients and growing predisposition to serious complications, the present review provides an update on the serotypic and genotypic profile of dengue outbreaks that have been witnessed by different zones of India between 2011 and 2017. Dividing the country into northern, southern, eastern, western, central and north-eastern zones, we describe discrete zone-specific distribution patterns of DENV serotypes and genotypes and observe simultaneous circulation of different DENV strains in different parts of the country. Random shifts in the genetic characteristics of the circulating strains and the widespread co- circulation of all four serotypes underscore the need for undertaking continuous and representative molecular surveillance of the circulating DENV strains across the country for prompt identification of emerging strains and novel mutants; gain insights into the formulation of Dengue vaccines and develop a clearer understanding of the molecular basis of immune evasion, disease epidemiology and pathogenesis.

Advancements in Managing Pure Ductal Carcinoma In Situ: An 18-Year Artificial Intelligence-Aided Analysis of 998 Patients

IntroductionThe integration of artificial intelligence (AI) in oncological diseases has opened new avenues for early cancer detection, accurate risk assessments, and personalized treatment protocols. The objective of our study was to describe the shift in the treatment indications and prognosis of ductal carcinoma in situ (DCIS) in a prospective cohort of 998 patients managed over 18 years at a single University Hospital in France. MethodsThis analysis included all patients managed for DCIS at the University Hospitals of Strasbourg between January 14, 2002, and December 18, 2019, from the prospective SENOMETRY cohort, which initially included 9599 patients with both in situ and invasive breast cancer. Data were analyzed using Onconum, an AI-based natural language processing tool, to extract structured information from medical records. ResultsThe incidence of DCIS remained stable at 65 new cases per year. The mean age at diagnosis increased from 55 years in 2002 to 61 years in 2019. There was a significant rise in high-grade DCIS (DIN3) cases from 25% to 35%. The re-excision rate decreased from 57% in 2002 to 18% in 2019. Most DCIS cases were managed with breast-conserving surgeries (682), while total mastectomies accounted for 385 cases. Sentinel lymph node biopsy was performed in 39% of cases, primarily in high-grade and multifocal DCIS. Specific mortality was 0%, with a recurrence rate of 2.2%, predominantly invasive and occurring earlier in high-grade DCIS. Discussion: Over 18 years, there has been a notable shift in the clinicopathological characteristics of DCIS, with an increase in patient age at diagnosis and higher histopathological grades. Therapeutic management evolved significantly, with reduced surgical margins and fewer adjuvant treatments, while maintaining low and stable recurrence rates. AI significantly enhanced data extraction and analysis efficiency, contributing to better clinical decision-making. ConclusionThe study confirms the possibility of therapeutic de-escalation in DCIS, supported by AI-driven data analysis, allowing individualized treatment approaches and leading to optimized patient outcomes.

Surface Variability Mapping and Roughness Analysis of the Moon Using a Coarse‐Graining Decomposition

AbstractThe lunar surface contains a wide variety of topographic shapes and features, each with different distributions and scales, and any analysis technique to objectively measure roughness must respect these qualities. Coarse‐graining is a naturally scale‐dependent filtering technique that preserves scale‐dependent symmetries and produces coarse elevation maps that gradually erase the smaller features from the original topography. In this study of the lunar surface, we present two surface variability metrics obtained from coarse‐graining lunar topography: fine elevation and coarse curvature. Both metrics are isotropic, deterministic, slope‐independent, and coordinate‐agnostic. Fine (detrended) elevation is acquired by subtracting the coarse elevation from the original topography and contains features that are smaller than the coarse‐graining length‐scale. Coarse curvature is the Laplacian of coarsened topography, and naturally quantifies the curvature at any scale and indicates whether a location is elevated or depressed relative to its neighborhood at that scale. We find that highlands and maria have distinct roughness characteristics at all length‐scales. Our topographic spectra reveal four scale‐breaks that mark characteristic shifts in surface roughness: 100, 300, 1,000, and 4,000 km. Comparing fine elevation distributions between maria and highlands, we show that maria fine elevation is biased toward smaller‐magnitude elevations and that the maria–highland discrepancies are more pronounced at larger length‐scales. We also provide local examples of selected regions to demonstrate that these metrics can successfully distinguish geological features of different length‐scales.

A Novel SERS Label-Free Sensing Strategy for DON and NIV: A DFT Study on the Interaction between DON/NIV and Ag/Au.

In this study, we propose a novel label-free detection strategy based on surface-enhanced Raman spectroscopy (SERS) for detecting deoxynivalenol (DON) and nivalenol (NIV), analyzing the interactions between these fungal toxins and Ag/Au substrates using density functional theory (DFT). The DFT calculation results indicate that the oxygen atoms in DON and NIV molecules exhibit high electronegativity, suggesting that they can serve as active sites in interaction with the metal surfaces in the SERS effect. By constructing DON/NIV-Ag6/Au6 complex models and evaluating their binding energies, we demonstrate the formation of stable complexes, showing characteristic frequency shifts, broadening, and selective enhancement in theoretical Raman spectra. The results indicate that the structural differences between DON and NIV lead to significant variations in the characteristic frequencies of their theoretical SERS spectra, providing a reproducible and interference-resistant method for the label-free detection of these fungal toxins. This work enhances the understanding of molecular-substrate interactions in SERS effects and provides a theoretical basis for the application of label-free SERS sensing strategies based on characteristic frequency shifts.

Related work analysis for determination of fatigue state based on eye movements monitoring

We have reviewed theoretical background of detecting functional state of fatigue based on the strategy of eye movements. Also, modern methods for assessing eye movements were considered. Based on our literature review, we can conclude that nowadays there are multitude numerical characteristics of eye movements, the dynamics of which can hypothetically make it possible to assess degree of fatigue. However, there are still no proposals for a method for determining the degree of fatigue based on an analysis of the strategy of eye movements. In this regard, according to the concepts of static and dynamic vision, it is proposed to consider the shift in the numerical characteristics of eye movements towards characteristics that reflect the strategy of dynamic vision as evidence of fatigue.

Experimental subshell vacancies in a multiply ionised Sn atom by heavy ion impact

The adoption of Heavy Ion PIXE for elemental quantification remains limited by the lack of fundamental atomic parameters needed for the calculation of X-ray production cross section data. Widely adapted theoretical models used for approximating ionisation cross sections, as well as other atomic physical parameters such as X-ray fluorescence yields, are calculated based on single-hole vacancy production post ion-atom impact. This renders the use of conventional ‘protonic’ models invalid for heavy ion-atom collisions. The degree to which Multiple Ionisation (MI) manifests in different heavy ion-atom collision symmetries significantly modifies atomic physical parameters. This is due to the significant number of introduced spectator vacancies in higher subshells, especially where near-symmetry is approached and MI is more pronounced. Knowledge of the mean number of vacancies in upper subshells is thus important for modifying atomic parameters that are needed for the translation of ionisation to X-ray production cross sections. In the present study, MI effects for Sn L-shell X-rays were studied using characteristic X-ray energy shifts measured using a standard PIXE spectrometer induced by Si, Cu and I projectile ions with incident energies up to 0.75 MeV/u. MI satellite distributions were studied using a Wavelength dispersive X-ray spectrometer (WDS) for high resolution PIXE, induced by C and Si projectile ions with incident ion energies up to 1.25 MeV/u. The mean number of subshell vacancies in the M- and N- shell for energy shifted Sn Lα X-ray lines were determined using both standard and high resolution PIXE spectrometers.

Direct evidence for a deprotonated lysine serving as a H-bond "acceptor" in a photoreceptor protein.

Deprotonation or suppression of the pKa of the amino group of a lysine sidechain is a widely recognized phenomenon whereby the sidechain amino group transiently can act as a nucleophile at the active site of enzymatic reactions. However, a deprotonated lysine and its molecular interactions have not been directly experimentally detected. Here, we demonstrate a deprotonated lysine stably serving as an "acceptor" in a H-bond between the photosensor protein RcaE and its chromophore. Signal splitting and trans-H-bond J coupling observed by NMR spectroscopy provide direct evidence that Lys261 is deprotonated and serves as a H-bond acceptor for the chromophore NH group. Quantum mechanical/molecular mechanical calculations also indicate that this H-bond exists stably. Interestingly, the sidechain amino group of the lysine can act as both donor and acceptor. The remarkable shift in the H-bond characteristics arises from a decrease in solvation, triggered by photoisomerization. Our results provide insights into the dual role of this lysine. This mechanism has broad implications for other biological reactions in which lysine plays a role.

Chilling or chemical induction of dormancy release in blackcurrant (Ribes nigrum) buds is associated with characteristic shifts in metabolite profiles.

This study reveals striking differences in the content and composition of hydrophilic and lipophilic compounds in blackcurrant buds (Ribes nigrum L., cv. Ben Klibreck) resulting from winter chill or chemical dormancy release following treatment with ERGER, a biostimulant used to promote uniform bud break. Buds exposed to high winter chill exhibited widespread shifts in metabolite profiles relative to buds that experience winter chill by growth under plastic. Specifically, extensive chilling resulted in significant reductions in storage lipids and phospholipids, and increases in galactolipids relative to buds that experienced lower chill. Similarly, buds exposed to greater chill exhibited higher levels of many amino acids and dipeptides, and nucleotides and nucleotide phosphates than those exposed to lower chilling hours. Low chill buds (IN) subjected to ERGER treatment exhibited shifts in metabolite profiles similar to those resembling high chill buds that were evident as soon as 3 days after treatment. We hypothesise that chilling induces a metabolic shift which primes bud outgrowth by mobilising lipophilic energy reserves, enhancing phosphate availability by switching from membrane phospholipids to galactolipids and enhancing the availability of free amino acids for de novo protein synthesis by increasing protein turnover. Our results additionally suggest that ERGER acts at least in part by priming metabolism for bud outgrowth. Finally, the metabolic differences presented highlight the potential for developing biochemical markers for dormancy status providing an alternative to time-consuming forcing experiments.

Advancing structural elucidation of conjugation drug metabolites in metabolite profiling with novel electron-activated dissociation.

This study focuses on the advantage of using the novel electron-activated dissociation (EAD) technology on the QTOF system for structural elucidation of conjugation metabolites. In drug metabolite identification, conceptual "boxes" are generally used to represent potential sites of modifications, which are proposed based on MS/MS data. Electron-activated dissociation (EAD) provides unique fragmentation patterns, potentially allowing for more precise localization of the metabolic modification sites compared to CID, particularly for conjugations. Known compounds were incubated with rat liver microsomes in the presence of nicotinamide adenine dinucleotide phosphate (NADPH), uridine dihosphate-glucuronic acid (UDPGA), and glutathione. Conjugation metabolites were analyzed using the QTOF system. High-resolution MS/MS spectra were collected using EAD and CID fragmentations along with TOF MS full scan for tested drugs and metabolites. Fragmentation patterns were compared to evaluate their efficiency in structural elucidation. Metabolite profiling identified conjugation metabolites (glucuronides and GSH adducts), using characteristic mass shifts. A comparison of EAD and CID fragmentation revealed EAD-specific fragments for most conjugates. EAD was able to break the relatively stable bonds on parent drug motifs while keeping relatively weak conjugation bonds intact, despite the generally low intensity of EAD. EAD effectively narrowed the conceptual "box" representing modification sites, providing more definitive information on conjugation sites and facilitating the structural elucidation of conjugated metabolites. EAD is a powerful tool for metabolite profiling in drug development, particularly for identifying conjugation sites. EAD-enabled MS/MS spectra offer a greater variety of signature fragments compared to CID, resulting in more comprehensive and unique structural information for metabolic modification analysis. Overall, EAD, complementary to CID, has the potential to narrow down potential modification sites, significantly enhancing the precision of conjugation metabolite structure elucidation.

Uncovering quantum characteristics of incipient evolutions at the photosynthetic oxygen evolving complex

Water oxidation of photosynthesis at the oxygen evolving complex (OEC) is driven by the polarization field induced by the photoelectric hole. By highlighting the role of the polarization field in reshaping the spin and orbit potentials, we reveal in this work the characteristics and underlying mechanism in the relatively simpler OEC evolutions within the states S0–S2 prior to the water oxidation. The characteristic shifts of the density of states (DOS) of the electron donor Mn atom are observed in the vicinity of the Fermi surface to occur with the spin flips of Mn atoms and the change in the Mn oxidation states during the electron transfer. Notably, the spin flips of Mn atoms point to the resulting spin configuration of the next states. It is found that the electron transfer tends to stabilize the catalyst OEC itself, whereas the proton transfer pushes the evolution forward by preparing a new electron donor, demonstrating the proton-coupled electron transfer. Meanwhile, it shows that the Mn–O bonds around the candidate Mn atom of the electron donor undergo characteristic changes in the bond lengths during the electron transfer. These concomitant phenomena uncovered in first-principle calculations characterize the essential equilibrium of the OEC between the state evolution and stability that forms the groundwork of the dynamic OEC cycles. In particular, the characteristic undulation of the DOS around the Fermi level occurring at the proton-coupled electron transfer can be used to reveal crucial processes in a wide range of realistic systems.

Increasing WNP tropical cyclone-related extreme precipitation over East Asia during boreal summer associated with PDO shift

Over the past two decades, there has been a significant shift in tropical cyclone (TC) activity in the western North Pacific (WNP) basin during the boreal summer. Our analysis of data spanning from 1979 to 2021 reveals significant shifts in the WNP TC characteristics and rainfall pattern variation. To deepen our understanding of TC-related precipitation dynamics, we expressly address the difference between TC-related core precipitation (TCP) and remote precipitation (TRP). The results show that TRP significantly impacts the East Asian (EA) continent, especially on the Korean Peninsula. Notably, TCP exhibits decadal variability, with a pronounced negative correlation identified between it and the Pacific decadal oscillation (PDO) following a strong climate shift. This pivotal shift was marked by the PDO first transitioning to its negative phase in 1997, a notable change since 1979, resulting in a marked increase in TC-related extreme rainfall over the EA area. Concurrently, the rising sea surface temperatures (SSTs) over the WNP have intensified the western Pacific subtropical high (WPSH) circulation. The easterly steering flow associated with the WPSH then strengthened, leading to the continental migration of TC trajectories, thereby intensifying TC-related extreme precipitation.

Computational framework for the generation of one-dimensional vascular models accounting for uncertainty in networks extracted from medical images.

One-dimensional (1D) cardiovascular models offer a non-invasive method to answer medical questions, including predictions of wave-reflection, shear stress, functional flow reserve, vascular resistance and compliance. This model type can predict patient-specific outcomes by solving 1D fluid dynamics equations in geometric networks extracted from medical images. However, the inherent uncertainty in in vivo imaging introduces variability in network size and vessel dimensions, affecting haemodynamic predictions. Understanding the influence of variation in image-derived properties is essential to assess the fidelity of model predictions. Numerous programs exist to render three-dimensional surfaces and construct vessel centrelines. Still, there is no exact way to generate vascular trees from the centrelines while accounting for uncertainty in data. This study introduces an innovative framework employing statistical change point analysis to generate labelled trees that encode vessel dimensions and their associated uncertainty from medical images. To test this framework, we explore the impact of uncertainty in 1D haemodynamic predictions in a systemic and pulmonary arterial network. Simulations explore haemodynamic variations resulting from changes in vessel dimensions and segmentation; the latter is achieved by analysing multiple segmentations of the same images. Results demonstrate the importance of accurately defining vessel radii and lengths when generating high-fidelity patient-specific haemodynamics models. KEY POINTS: This study introduces novel algorithms for generating labelled directed trees from medical images, focusing on accurate junction node placement and radius extraction using change points to provide haemodynamic predictions with uncertainty within expected measurement error. Geometric features, such as vessel dimension (length and radius) and network size, significantly impact pressure and flow predictions in both pulmonary and aortic arterial networks. Standardizing networks to a consistent number of vessels is crucial for meaningful comparisons and decreases haemodynamic uncertainty. Change points are valuable to understanding structural transitions in vascular data, providing an automated and efficient way to detect shifts in vessel characteristics and ensure reliable extraction of representative vessel radii.

Green synthesis of silver nanoparticles from Manilkara zapota leaf extract for the detection of aminoglycoside antibiotics and other applications.

Antibiotics of aminoglycoside (AMG) class, such as streptomycin (STR), have been widely used to treat infectious diseases caused by Gram-negative bacteria in livestock and humans. In this study, a selective and sensitive colorimetric probe for the determination of STR was proposed based on eco-friendly green synthesized AgNPs from the leaf extract of Manilkara zapota. The mechanism for the detection of STR is based on the electrostatic interaction of opposite charges between negatively charged silver nanoparticle-Manilkara zapota leaf (AgNP-MZL) and STR, causing an aggregation-induced characteristic shift of the SPR band (from 390 nm to 570 nm wavelength) of AgNP-MZL. The morphology, size distribution and optical properties of AgNP-MZL were characterized using UV/visible absorption spectroscopy, FTIR spectroscopy, XRD, DLS, zeta-potential measurements and TEM. The selective determination of STR was experimentally confirmed by performing controlled testing with other classes of antibiotics. To test the sensitivity level of this method, the ratio of these two A 390/A 570 absorbance wavelengths was selected to provide a linear concentration plot between 5 and 100 ng mL-1 STR. The LOD and LOQ were calculated to be 3.5 ng mL-1 and 26.8 ng mL-1, respectively. Good precision was evaluated with a standard deviation of 0.45 ng mL-1 and a relative standard deviation of 2.0% (intraday) and 2.42% (interday) at 10 ng mL-1 for 3 replicate measurements. Advantages of the green synthesis of AgNP-MZL include its eco-friendly nature and it is easy, efficient, cost effective and selective for the detection of the AMG class of antibiotics, i.e. STR, in agricultural and environmental samples.

Polygenic scores for psychiatric disorders associate with year of first bipolar disorder diagnosis: A register-based study between 1972 and 2016

The diagnostic criteria of bipolar disorder (BD) have changed over time. To test if these changes are reflected in the polygenic profile in BD, we studied the association between first BD diagnosis year (during 1972–2016) and polygenic scores (PGS) for psychiatric disorders in BD patients (N = 3,818). We found significant associations between diagnosis year and PGS for BD, depression, and attention deficit hyperactivity disorder (ADHD). The PGS remained largely stable over time in BD type 1, while changes were observed in BD type 2. These findings bear significance not only for genetic research but also for clinical practise, as shifts in patient characteristics can influence treatment response.

Serum lipidomic profiling of dairy calves fed milk replacers containing animal or vegetable fats

Vegetable fat blends are commonly used as fat sources in milk replacers (MR) for calves, but their composition differs considerably from that of bovine milk fat. The aim of this study was to investigate the serum lipid profile of pre-weaned calves fed twice-daily MR containing 30% fat (% DM). Upon arrival, 30 male Holstein-Friesian calves (BW = 45.6 ± 4.0 kg, age = 2.29 ± 0.8 d) were randomly assigned to 2 experimental diets (n = 15 per treatment): one MR was derived from either vegetable fats (VG; 80% rapeseed and 20% coconut fats) or animal fats (AN; 65% Packer's lard and 35% dairy cream). The 2 MR formulas contained 30% fat, 24% CP, and 36% lactose. Calves were housed indoors in individual pens with ad libitum access to chopped straw and water. Daily milk allowances were 6.0 L from d 1 to 5, 7.0 L from d 6 to 9, and 8.0 L from d 10 to 35, divided into 2 equal meals and prepared at 13.5% solids. An untargeted liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method was employed to analyze the lipid profiles in the serum of calves sampled from the jugular vein at 35 d of age. In total, 594 lipids were characterized, comprising 25 different lipid classes. Principal component analysis (PCA) showed significant separation between VG and AN, indicating different lipid profiles in the serum. An orthogonal partial least squares discriminant analysis (OPLS-DA) classification model was used to further validate the distinction between the 2 treatment groups. The model exhibited a robust class separation and high predictive accuracy. Using a Volcano plot (fold change threshold ≥1.5 and false discovery rate ≤0.05), it was observed that calves fed AN had higher levels of 39 lipid species in serum than calves fed VG, whereas 171 lipid species were lower in the AN group. Lipid classes, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), triglycerides (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), were different. In particular, PC and PE were observed at lower levels in calves fed AN, possibly indicating shifts in cell membrane characteristics, intracellular signaling, and liver functions. In addition, a decrease in certain triglyceride (TG) species was observed in calves fed AN, including a decrease in TG species such as TG 36:0 and TG 38:0, possibly related to variations in the content of certain fatty acids (FA) within the AN MR, such as C10:0, C12:0, C14:0, and C18:0 compared with the VG MR. Calves fed AN had lower levels of LPC and LPE, and lyso-phosphatidylinositol (LPI), SM, and phosphatidylinositol (PI) species than calves fed VG, suggesting shifts in lipoprotein and lipid metabolic pathways. In conclusion, these results deepen the understanding of how lipid sources in MR can modulate the serum lipidome profiles of dairy calves.