In recent decades, there has been a concerning and consistent rise in the incidence of cancer, posing a significant threat to human health and overall quality of life. The transferrin receptor (TfR) ...is one of the most crucial protein biomarkers observed to be overexpressed in various cancers. This study reports on the development of a novel voltammetric immunosensor for TfR detection. The electrochemical platform was made up of a glassy carbon electrode (GCE) functionalized with gold nanoparticles (AuNPs), on which anti-TfR was immobilized. The surface characteristics and electrochemical behaviors of the modified electrodes were comprehensively investigated through scanning electron microscopy, XPS, Raman spectroscopy FT-IR, electrochemical cyclic voltammetry and impedance spectroscopy. The developed immunosensor exhibited robust analytical performance with TfR fortified buffer solution, showing a linear range (LR) response from 0.01 to 3000 μg/mL, with a limit of detection (LOD) of 0.01 μg/mL and reproducibility (RSD <4 %). The fabricated sensor demonstrated high reproducibility and selectivity when subjected to testing with various types of interfering proteins. The immunosensor designed for TfR detection demonstrated several advantageous features, such as being cost-effective and requiring a small volume of test sample making it highly suitable for point-of-care applications.
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Where and When do Species Interactions Set Range Limits? Louthan, Allison M.; Doak, Daniel F.; Angert, Amy L.
Trends in ecology & evolution (Amsterdam),
December 2015, 2015-Dec, 2015-12-00, 20151201, Volume:
30, Issue:
12
Journal Article
Peer reviewed
A long-standing theory, originating with Darwin, suggests that abiotic forces set species range limits at high latitude, high elevation, and other abiotically ‘stressful’ areas, while species ...interactions set range limits in apparently more benign regions. This theory is of considerable importance for both basic and applied ecology, and while it is often assumed to be a ubiquitous pattern, it has not been clearly defined or broadly tested. We review tests of this idea and dissect how the strength of species interactions must vary across stress gradients to generate the predicted pattern. We conclude by suggesting approaches to better test this theory, which will deepen our understanding of the forces that determine species ranges and govern responses to climate change.
Both climate and species interactions set species range limits, but it is unclear when each is most important.
An old hypothesis, first proposed by Darwin, suggests that abiotic factors should be key drivers of limits in abiotically stressful areas, and species interactions should dominate in abiotically benign areas.
Four distinct mechanisms, ranging from per-capita effects to community-level synergies, could result in differential importance of species interactions across stress gradients.
These mechanisms, operating alone or in tandem, can result in patterns consistent or inconsistent with Darwin's hypothesis, depending on the strength and direction of effects.
The most robust test of this hypothesis, not to date performed in any study, is to analyze how sensitive range limit location is to changes in the strength of one or more species interactions and also to abiotic stressors.
Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder ...mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.
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•A human CLP1 mutation causes brain and motor neuron degeneration•Mutation impairs kinase activity, nuclear localization, and TSEN complex assembly•Patient iNeurons have accumulated pre-tRNA and reduced mature tRNA•Clp1 mutant zebrafish display p53-dependent neurodegeneration
A mutation in the human RNA kinase Clp1 perturbs tRNA biogenesis and promotes susceptibility to apoptosis, leading to a complex neurological phenotype.
Legumes are able to form a symbiotic relationship with nitrogen-fixing soil bacteria called rhizobia. The result of this symbiosis is to form nodules on the plant root, within which the bacteria can ...convert atmospheric nitrogen into ammonia that can be used by the plant. Establishment of a successful symbiosis requires the two symbiotic partners to be compatible with each other throughout the process of symbiotic development. However, incompatibility frequently occurs, such that a bacterial strain is unable to nodulate a particular host plant or forms nodules that are incapable of fixing nitrogen. Genetic and molecular mechanisms that regulate symbiotic specificity are diverse, involving a wide range of host and bacterial genes/signals with various modes of action. In this review, we will provide an update on our current knowledge of how the recognition specificity has evolved in the context of symbiosis signaling and plant immunity.
•We compared sensitivities and specificities of the SARS-CoV-2 RT-LAMP with RT-qPCR.•Up to the 9th day of onset, RT-LAMP has the same diagnostic sensitivity as RT-qPCR.•After the 10th day of onset, ...the positivity of RT-LAMP decreased considerably.•The limit of detection of RT-LAMP was 6.7 SARS-CoV-2 RNA copies/reaction.
Reverse transcription loop-mediated isothermal amplification (RT-LAMP) has been validated to diagnose several viral infections. However, its diagnostic accuracy in detecting SARS-CoV-2 in real-life clinical settings remains unclear. This study aimed to determine the diagnostic sensitivity and specificity of RT-LAMP compared to reverse transcription-quantitative polymerase chain reaction (RT-qPCR) over the disease course of COVID-19.
A total of 124 nasopharyngeal swab samples obtained from 24 COVID-19 patients were tested by RT-LAMP and RT-qPCR. Sensitivities and specificities of RT-LAMP compared with RT-qPCR were analyzed as a function of time from onset.
Up to the 9th day after onset, the RT-LAMP had a positivity of 92.8%, and the sensitivity and specificity compared with RT-qPCR was 100%. However, after the 10th day after onset, the positivity of RT-LAMP decreased to less than 25%, and the concordance of positivity between the two methods was below 60%. The limit of detection of RT-LAMP was 6.7 copies/reaction.
Until the 9th day after the onset of symptoms, RT-LAMP had the same diagnostic accuracy as RT-qPCR. These findings suggest that RT-LAMP can be used as a diagnostic tool for COVID-19 as an alternative to RT-qPCR in the acute symptomatic phase of COVID-19.
Mitogen-activated protein kinases (MAPKs) play critical roles in the induction of numerous cytokines, chemokines, and inflammatory mediators that mobilize the immune system to counter pathogenic ...infections. Dual-specificity phosphatase 1 (DUSP1) is a member of the dual-specificity phosphatases that inactivates MAPKs through a negative-feedback mechanism. Here, we report that in response to viral and bacterial infections, not only the DUSP1 transcript but also its
-methyladenosine (m
A) levels rapidly increase together with that of the m
A reader protein YTHDF2, resulting in enhanced YTHDF2-mediated DUSP1 transcript degradation. The knockdown of DUSP1 promotes p38 and Jun N-terminal kinase (JNK) phosphorylation and activation, thus increasing the expression of innate immune response genes, including the interleukin-1β (IL-1β), colony-stimulating factor 3 (CSF3), transglutaminase 2 (TGM2), and proto-oncogene tyrosine-protein kinase Src (SRC) genes. Similarly, the knockdown of the m
A eraser ALKBH5 increases the DUSP1 transcript m
A level, resulting in accelerated transcript degradation, the activation of p38 and JNK, and the enhanced expression of IL-1β, CSF3, TGM2, and SRC. These results demonstrate that m
A and the reader protein YTHDF2 orchestrate optimal innate immune responses during viral and bacterial infections by downregulating the expression of a negative regulator, DUSP1, of the p38 and JNK pathways that are central to innate immune responses against pathogenic infections.
Innate immunity is central to controlling pathogenic infections and maintaining the homeostasis of the host. In this study, we have revealed a novel mechanism regulating innate immune responses during viral and bacterial infections. We have found that
-methyladenosine (m
A) and the reader protein YTHDF2 regulate dual-specificity phosphatase 1, a negative regulator of the mitogen-activated protein kinases p38 and JNK, to maximize innate immune responses during viral and bacterial infections. These results provide novel insights into the mechanism regulating innate immunity, which could help in the development of novel approaches for controlling pathogenic infections.
There is now overwhelming experimental and clinical evidence that atherosclerosis is a chronic inflammatory disease. Lessons from genome-wide association studies, advanced in vivo imaging techniques, ...transgenic lineage tracing mice, and clinical interventional studies have shown that both innate and adaptive immune mechanisms can accelerate or curb atherosclerosis. Here, we summarize and discuss the pathogenesis of atherosclerosis with a focus on adaptive immunity. We discuss some limitations of animal models and the need for models that are tailored to better translate to human atherosclerosis and ultimately progress in prevention and treatment.
Central venous catheter thrombosis can cause venous obstruction and pulmonary embolism. To determine the extent to which catheter thrombosis is triggered by the contact or extrinsic pathway of ...coagulation, we used antisense oligonucleotides (ASOs) to selectively knock down factor (f)XII, fXI, or high-molecular-weight kininogen (HK), key components of the contact pathway, or fVII, which is essential for the extrinsic pathway. Knockdown of contact pathway components prolonged the activated partial thromboplastin time and decreased target protein activity levels by over 90%, whereas fVII knockdown prolonged the prothrombin time and reduced fVII activity to a similar extent. Using a rabbit model of catheter thrombosis, catheters implanted in the jugular vein were assessed daily until they occluded, up to a maximum of 35 days. Compared with control, fXII and fXI ASO treatment prolonged the time to catheter occlusion by 2.2- and 2.3-fold, respectively. In contrast, both HK and fVII knockdown did not significantly prolong the time to occlusion, and dual treatment with fVII- and fXI-directed ASOs produced a time to occlusion similar to that with the fXI ASO alone. These findings suggest that catheter thrombosis is triggered via the contact pathway and identify fXII and fXI as potential targets to attenuate this complication.
•Antisense oligonucleotides reduce levels of target hepatic mRNA and protein and decrease clotting activity in rabbits.•Selective depletion of factors XI and XII in rabbits attenuates catheter thrombosis, whereas factor VII depletion does not.
Regulatory T (Treg) cell identity is defined by the lineage-specifying transcription factor (TF) Foxp3. Here we examined mechanisms of Foxp3 function by leveraging naturally occurring genetic ...variation in wild-derived inbred mice, which enables the identification of DNA sequence motifs driving epigenetic features. Chromatin accessibility, TF binding, and gene expression patterns in resting and activated subsets of Treg cells, conventional CD4 T cells, and cells expressing a Foxp3 reporter null allele revealed that the majority of Foxp3-dependent changes occurred at sites not bound by Foxp3. Chromatin accessibility of these indirect Foxp3 targets depended on the presence of DNA binding motifs for other TFs, including TCF1. Foxp3 expression correlated with decreased TCF1 and reduced accessibility of TCF1-bound chromatin regions. Deleting one copy of the Tcf7 gene recapitulated Foxp3-dependent negative regulation of chromatin accessibility. Thus, Foxp3 defines Treg cell identity in a largely indirect manner by fine-tuning the activity of other major chromatin remodeling TFs such as TCF1.
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•Forkhead motifs affect Foxp3 binding but not chromatin accessibility•Foxp3-dependent chromatin accessibility changes occur at sites not bound by Foxp3•Foxp3 downregulates TCF1 and reduces accessibility of TCF1-bound chromatin•Foxp3-dependent intermediaries define Treg cell epigenetic identity
Regulatory T (Treg) cell identity is defined by the lineage-specifying transcription factor (TF) Foxp3. van der Veeken et al. leverage naturally occurring genetic variation in wild-derived inbred mice and reveal that Foxp3 works in a largely indirect manner by fine-tuning the activity of other transcription factors, including TCF1.
While there is a clear demand for scenarios that provide alternative states in biodiversity with respect to future emissions, a thorough analysis and communication of the associated uncertainties is ...still missing. Here, we modelled the global distribution of ~11,500 amphibian, bird and mammal species and project their climatic suitability into the time horizon 2050 and 2070, while varying the input data used. By this, we explore the uncertainties originating from selecting species distribution models (SDMs), dispersal strategies, global circulation models (GCMs), and representative concentration pathways (RCPs). We demonstrate the overwhelming influence of SDMs and RCPs on future biodiversity projections, followed by dispersal strategies and GCMs. The relative importance of each component varies in space but also with the selected sensitivity metrics and with species' range size. Overall, this means using multiple SDMs, RCPs, dispersal assumptions and GCMs is a necessity in any biodiversity scenario assessment, to explicitly report associated uncertainties.
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