A single-mode-fiber (SMF)-multimode-fiber (MMF)-tri-core-fiber (TCF) Michelson probe structure is proposed for trace detection of canine distemper virus (CDV). One end of the TCF is cut flat and fused with the multimode fiber, and the other end is coated with a silver film to enhance the reflection, and an optic-fiber sensing probe with SMF-MMF-TCF structure is obtained. The (PDDA/PSS) 3 multilayer film is modified on the surface of the fiber by layer-by-layer self-assembly method as a polyelectrolyte binder to immobilize CDV antibodies to form a (PDDA/PSS) 3/CDV antibody composite membrane for specific detection of CDV antigens. The response-recovery test of the sensor is performed to verify its repeatability. The detection limit, the sensitivity, and the linear fitting degree for CDV antigen are 0.1236 pg/ml, 1.1776 dB/(pg/ml), and 0.9899, respectively. At the same time, the stability, selectivity, and clinical samples of the sensors were also verified.
Children fast-map new words to their referents early on but do not show robust retention until much later. This paper examines whether children’s interest in a natural category relates to retention of newly learned words in that category. German-speaking 24-month-olds and 38-month-olds (n = 88, 41 female) were trained on novel word-object-associations from different categories. Pupillary arousal and parental reports served as indices of interest in the objects and categories presented. Recognition and retention were tested directly after exposure, five minutes later, and 24 hours later. Both younger and older children showed successful word-object recognition and retention. Furthermore, interest in the category modulates young children’s recognition and retention of newly learned word-object associations from semantic categories across ages.
Herein we report a condition-controlled divergent synthesis of spiro indene-2,1’-isoindolinones and spiro isochroman-3,1’-isoindolinones through cobalt-catalyzed formal [4 + 1] and [4 + 1 + 1] spirocyclization of aromatic amides with 2-diazo-1H-indene-1,3(2H)-dione. When the reaction is carried out under air in ethyl acetate, spiro indene-2,1’-isoindolinones are formed through Co(II)-catalyzed C−H/N−H [4 + 1] spirocyclization. When the reaction is run under O2 in CH3CN, on the other hand, spiro isochroman-3,1’-isoindolinones are generated through Baeyer-Villiger oxidation of the in situ formed spiro indene-2,1’-isoindolinones with O2 as a cheaper and environmental-friendly oxygen source. In general, these protocols have advantages such as using non-precious and earth-abundant metal catalyst, no extra additive, high efficiency and regioselectivity. A gram-scale synthesis and the removal of the directing group further highlight its utility.
A one-pot synthesis of vicinal diamines using indoles, pyrazoles, and phenothiazines in a tandem multi-component reaction is developed. The utilization of a copper-iodine co-catalytic system enables the generation of a diverse range of vicinal diaminoindoles with good selectivity and moderate to good yields. An attractive aspect of this method is that it can be conducted under mild and environmentally friendly conditions, showcasing its potential as an alternative approach for synthesizing vicinal diamines. Moreover, the use of a multicomponent tandem reaction highlights the power and versatility of such strategies in synthetic chemistry.
A phosphine-catalyzed [4+3] annulation between dinucleophilic indole derivatives and Morita−Baylis−Hillman (MBH) carbonates was discovered by using the N1 and N4′ or C4′ nucleophilicities of indole precursors, which provides an efficient and facile access to in-dole-1,2-fused 1,4-diazepinones and azepines in good to high yields in one step, in which indoles act as four atom synthons. Various transformations of products illustrate promising applications of the given protocols.
Sepsis is a life-threatening organ dysfunction that results from dysregulated host response to infection. Multiple organ system dysfunction syndromes are prevalent among septic patients and are essential hallmarks of sepsis diagnosis. These syndromes involve failure of the pulmonary, hepatic, circulatory, renal, gastrointestinal and central nervous systems. Neurological dysfunction is part of this syndrome and has gained research attention recently . Sepsis induces neuroinflammation, BBB disruption, cerebral hypoxia, neuronal mitochondrial dysfunction and cell death causing sepsis-associated encephalopathy (SAE). These pathological consequences lead to short- and long-term neurobehavioral deficits. Till now there is no specific treatment that directly improves SAE and its associated behavioral impairments. In this review, we discuss the underlying mechanisms of sepsis-induced brain injury with a focus on the latest progress regarding neuroprotective eﬀects of SIRT1 (silent mating type information regulation-2 homologue-1). SIRT1 is an NAD+-dependent class III protein deacetylase. It is able to modulate multiple downstream signals (including NF-κB, HMGB, AMPK, PGC1α and FoxO) which are involved in the development of SAE by its deacetylation activity. There are multiple recent studies showing the neuroprotective eﬀects of SIRT1 in neuroinﬂammation related diseases. The proposed neuroprotective action of SIRT1 is meant to bring a promising therapeutic strategy for managing SAE and ameliorating its related behavioural deficits.
Psychopathy is characterized by glibness and superficial charm, as well as a lack of empathy, guilt, and remorse, and is often accompanied by antisocial behavior. The cerebral bases of this syndrome have been mostly studied in violent subjects or those with a criminal history. However, the antisocial component of psychopathy is not central to its conceptualization and, in fact, psychopathic traits are present in well-adjusted, non-criminal individuals within the general population. Interestingly, certain psychopathy characteristics appear to be particularly pronounced in some groups or professions. Importantly, as these so-called adaptive or successful psychopaths do not show antisocial tendencies or have significant psychiatric comorbidities, they may represent an ideal population to study this trait. Here we investigated such a group, specifically elite female judo athletes, and compared them to matched non-athletes. Participants completed psychopathy, anger, perspective-taking and empathic concern questionnaires and underwent structural magnetic resonance imaging (MRI). Grey matter density (GMD) was computed using voxel-based morphometry from the T1-weighted images. Athletes scored significantly higher in primary psychopathy and anger, and lower in empathy and perspective taking. They also exhibited smaller GMD in the right Temporal Pole, left Occipital Cortex, and left Amygdala/Hippocampus. GMD values for the latter cluster significantly correlated with primary psychopathy scores across both groups. These results confirm and extend previous findings to a little-studied population and provide support for the conceptualization of psychopathy as a dimensional personality trait which, not only is not necessarily associated with antisocial behavior, but may potentially have adaptive value.
For the first time, the 2022 CASP (Critical Assessment of Structure Prediction) community experiment included a section on computing multiple conformations for protein and RNA structures. There was full or partial success in reproducing the ensembles for four of the nine targets, an encouraging result. For protein structures, enhanced sampling with variations of the AlphaFold2 deep learning method was by far the most effective approach. One substantial conformational change caused by a single mutation across a complex interface was accurately reproduced. In two other assembly modeling cases, methods succeeded in sampling conformations near to the experimental ones even though environmental factors were not included in the calculations. An experimentally derived flexibility ensemble allowed a single accurate RNA structure model to be identified. Difficulties included how to handle sparse or low-resolution experimental data and the current lack of effective methods for modeling RNA/protein complexes. However, these and other obstacles appear addressable.
Background Understanding the cellular host factors that promote and inhibit viral entry is important for identifying viral countermeasures. CRISPR whole genome screens can be used to rapidly discover host factors that contribute to or impair viral entry. However, when using the live viruses and cellular lethality for selection, these screens can identify an overwhelming number of genes without specificity for the stage of the viral infection cycle. New screening methods are needed to identify host machinery contributing to specific steps of viral infection. Here, we developed a CRISPR whole genome screen and counter screen strategy based on a pseudoviral platform that allowed identification of genes specific to SARS-CoV-2 spike and vesicular stomatitis virus glycoprotein VSV-G mediated entry. Methods To focus the screen onto the entry step, we used non-lytic fluorescent reporters in combination with a comparative counter screen strategy to distinguish host genes affecting the pseudoviral reporter from those unique to envelope-mediated entry. Screening of SARS-CoV-2 spike and VSV-G on the same lentiviral pseudovirus allowed identification of entry-specific genes relative to genes associated with retro-transcription, integration, and reporter expression from the lentiviral pseudovirus. Second, a Cre-Gag fusion protein in the pseudovirus was used to bypass retro-transcription and integration by directly activating a floxed GFP reporter upon entry to reduce the number of gene hits and increase specificity for viral entry. Results Our approach correctly identified SARS-CoV-2 and VSV-G receptors ACE2 and LDLR, respectively and distinguished genes associated with retroviral reporter expression from envelope-mediated entry. Moreover, the CRE-Gag fusion/flox reporter increased the screen specificity for viral entry associated genes. Validation of a few hits demonstrates that this approach distinguishes envelope-specific host factors from genes affecting reporter expression. Conclusion Overall, this approach provides a new strategy for identifying host genes influencing viral entry without the confounding complexity of live-viral screens which produce long gene lists associated with all aspects of viral pathogenesis and replication. This approach provides a pathway for increasing the specificity of CRISPR whole genome screens for identifying host genes contributing to specific steps in viral infection.
Many clinical and research efforts aim to develop antidepressant drugs for those suffering from major depressive disorder (MDD). Yet even today, the available treatments are suboptimal and unpredictable, with a significant proportion of patients enduring multiple drug attempts and adverse side effects before a successful response; and for many patients, no response at all. Thus, a clearer understanding of the mechanisms underlying MDD is necessary. In the “Brain Development and Disease” class of our Master’s program in Cognitive Sciences, we ask students to collect data about the expression of a gene whose altered expression and/or function is related to a brain disorder. The students’ final exam assignment consists of writing a research article in which the collected data are discussed in relation to the relevant disorder. In the course of one of these assignments, we identified the FKBP5 gene as a key player uniting two major hypotheses of MDD pathogenesis and treatment response. FKBP5 controls biological processes including immunoregulation and glucocorticoid function, both of which are separately implicated in the development and prognosis of MDD. Gene expression analyses from the human, non-human primate, and mouse Allen Brain Atlases revealed that FKBP5 is expressed in brain regions involved in MDD, particularly at ages susceptible to early-life stressors. Data re-analysis from published studies confirmed that FKBP5 expression is upregulated in relevant brain regions in human MDD and preclinical mouse models of MDD. Our experience shows that classes engaging students in data collection and analysis projects may effectively result in novel data-driven hypotheses.
Phlebia genus is a relevant group of fungi with crucial role in numerous ecosystems. In tropical and subtropical areas this genus allows the efficient degradation of lignin and carbon recovery; however, the majority of these fungal species remains undiscovered. The main purpose of this work was to determine the enzymatic activity of extracellular proteins of a novel Phlebia floridensis strain isolated in Yucatan Peninsula, Mexico. The results that are reported here demonstrate that soluble protein extract of P. floridensis can degrade a broad spectrum of recalcitrant compounds. This induced protein extract is able to modify not only phenolic and non-phenolic compounds, but also anthroquinone dyes, even without addition of exogenous hydrogen peroxide. Using LC-MS/MS, we were able to identify a novel chloroperoxidase in enzymatic extract. As far as we know, this is the first report about the presence of this type of enzyme in Phlebia genus.
Polycyclic N-heterocycles are very important scaffolds in biomedicinal chemistry and materials science. Intramolecular alkyne hy-droamination is a powerful method for the construction of N-heterocycles. In the last two decades, copper-catalyzed domino reac-tions based on intramolecular alkyne hydroamination has emerged as a robust strategy for assembling various polycyclic N-heterocycles. Great progress has been achieved in this area. This short review covers the advances made in copper-catalyzed domino synthesis of polycyclic N-heterocycles based on this strategy from 2008 to 2023, and will hopefully serve as an inspiration towards the exploration of new copper-catalyzed versions of the transformation. The domino transformations are introduced and discussed from five aspects according to the different key processes involved in these reactions.
Introductions of invasive species to new environments often result in rapid rates of trait evolution. While in some cases these evolutionary transitions are adaptive and driven by natural selection, they can also result from patterns of genetic and phenotypic variation associated with the invasion history. Here, we examined the brown anole (Anolis sagrei), a widespread invasive lizard for which genetic data have helped trace the sources of non-native populations. We focused on the dewlap, a complex signaling trait known to be subject to multiple selective pressures. We measured dewlap reflectance, pattern, and size in 30 non-native populations across the southeastern United States. As well, we quantified environmental variables known to influence dewlap signal effectiveness, such as canopy openness. Further, we used genome-wide data to estimate genetic ancestry, perform association mapping, and test for signatures of selection. We found that among-population variation in dewlap characteristics was best explained by genetic ancestry. This result was supported by genome-wide association mapping, which identified several ancestry-specific loci associated with dewlap traits. Despite the strong imprint of this aspect of the invasion history on dewlap variation, we also detected significant relationships between dewlap traits and local environmental conditions. However, we found limited evidence that dewlap-associated genetic variants have been subject to selection. Our study emphasizes the importance of genetic ancestry and admixture in shaping phenotypes during biological invasion, while leaving the role of selection unresolved, likely due to the polygenic genetic architecture of dewlaps and selection acting on many genes of small effect.
Historically, patients suffering from pathological narcissism, including narcissistic personality disorder (NPD), were considered challenging and hard to treat. Since the second half of the 20th century new treatments have been developing heralding a growing hope that transformative treatment of patients with pathological narcissism is possible. Recent developments of phenomenology, childhood antecedents, longitudinal course, and putative mechanisms inspired a greater hope as well. This invites clinicians and researchers to take an approach that is evidence-based, destigmatizing, and collaborative that considers that at least some of the treatment challenges as co-created by both the therapist and the patient. Further, new treatments add hope by ameliorating such challenges of patients with pathological narcissism as fragile alliance, limitations of reflectiveness and grieving. Novel treatments are evidence- and principles-based and different approaches to effective treatment development are described. Inspired by these developments in the field, this Issue of the Journal of Clinical Psychology: In Session was conceived as an opportunity for clinicians from different treatment approaches to come together and share their experiences in treating patients with pathological narcissism. The hope is to find common language to understand these patients and their treatment, understand what contributes to change, as well as learn from commonalities and differences among these treatments. In doing so, this Issue is hoping to promote destigmatizing, pragmatic approach that prioritizes evidence-based efforts to understand the patient and collaborative approach to promoting change.
Cubic silicon carbide (3C-SiC) has superior mobility and thermal conduction than that of widely applied hexagonal 4H-SiC. Moreover, much lower concentration of interfacial traps between insulating oxide gate and 3C-SiC helps fabricate reliable and long-life devices like metal-oxide-semiconductor field effect transistors (MOSFETs). However, the growth of high quality and wafer-scale 3C-SiC crystals has remained a big challenge up to now despite of decades-long efforts by researchers because of its easy transformation into other polytypes during growth, limiting the development of 3C-SiC based devices. Herein, we report that 3C-SiC can be made thermodynamically favored from nucleation to growth on a 4H-SiC substrate by top-seeded solution growth technique (TSSG), beyond what’s expected by classic nucleation theory. This enables the steady growth of high-quality and large-size 3C-SiC crystals (2~4-inch in diameter and 4.0~10.0 mm in thickness) sustainable. The as-grown 3C-SiC crystals are free of other polytypes and have high crystalline quality. Our findings broaden the mechanism of hetero-seed crystal growth and provide a feasible route to mass production of 3C-SiC crystals, offering new opportunities to develop power electronic devices potentially with better performances than those based on 4H-SiC.
The development of winter-tolerant safflower genotypes is crucial for the improvement of global safflower agriculture. The aim of the present study was to determine the cold tolerance abilities and some agricultural characteristics of advanced safflower genotypes. For this purpose, ten advanced safflower genotypes were used in four different locations. The experimental design was a randomized complete block design with three replications. Winter survival and agricultural characters were significantly affected by growing season, location and genotype. Winter survival varies between 86.43% and 93.91% among the genotypes, and it was promising for winter sowing. As the average of two years, the highest oil content (36.25%) was observed in genotype EC21 and it was followed by genotypes EC11 (35.51%) and EC20 (35.49%). As with the seed yield, the high winter survival of genotypes with high oil content is highly promising in terms of winter sowing. Safflower should be grown in winter with mild temperature regions for high seed yield and sustainable safflower production. Therefore, this study focused on winter-tolerant genotypes that are superior one in terms of seed yield and oil content.