Electrochemical aptamer-based (EAB) sensors are a molecular measurement platform that enables the continuous, real-time measurement of a wide range of drugs and biomarkers in situ in the living body. EAB sensors are fabricated by depositing a thiol-modified, target-binding aptamer on the surface of a gold electrode, followed by backfilling with an alkanethiol to form a self-assembled monolayer. And while the majority of previously described EAB sensors have employed hydroxyl-terminated monolayers, a handful of studies have shown that altering the monolayer headgroup can strongly affect sensor performance. Here, using 4 different EAB sensors, we show that the mixed monolayers composed of mixtures of 6-carbon hydroxyl-terminated thiols and varying amounts of either 6- or 8-carbon, carboxylate-terminated thiols lead to improved EAB sensor performance. Specifically, the use of such mixed monolayers enhances the signal gain (the relative change in the signal seen upon target addition) for all tested sensors, often by several fold, both in buffer and whole blood at room temperature or physiological temperatures. Moreover, these improvements in gain are achieved without significant changes in the aptamer affinity or the stability of the resulting sensors. In addition to proving a ready means of improving EAB sensor performance, these results suggest that exploration of the chemistry of the electrode surface employed in such sensors could prove to be a fruitful means of advancing this unique in vivo sensing technology.
Abstract: Despite increasing racial diversity in the United States, and the particular growth of multiracial populations, questions about how children perceive others’ (bi)racial identities remain poorly understood. In two preregistered studies, we asked White and racially minoritized American children (N = 157; 4–11‐years old) and White and multiracial adults (N = 226) how acceptable it was for monoracial people (Black or White; Study 1) and/or biracial people (Black–White; Studies 1 and 2) to claim either a monoracial or biracial identity. Consistent with past research with adults, children said that monoracial people should claim (only) the monoracial identity which matched their ancestry. Judgements about biracial identity were more variable. White and multiracial adults (Study 2) reported that biracial targets could claim a racial identity that matched either or both of their parents, with biracial claims being evaluated most positively. Exploratory analyses on children's judgements about biracial people's identity claims (Study 1) revealed different patterns of development for White children and children from minoritized backgrounds. Whereas White children became more likely with age to report that all identity claims were acceptable, children from racially minoritized groups became more likely with age to endorse biracial targets who claimed a biracial identity. These findings suggest that children's own racial background and age may have a larger impact on their perceptions of biracial people's identities, compared to their perceptions of monoracial people's identities.
Studying comorbidities in early onset Alzheimer disease (AD) may provide an advantageous perspective on their pathogenesis because aging factors may be largely inoperative for these subjects. We compared AD comorbidities between early-onset sporadic cases and American and Colombian cases with PSEN1 mutations. AD neuropathological changes (ADNC) were very severe in all groups but more severe in the PSEN1 groups. Lewy body disease and cerebral white matter rarefaction were the most common (up to 60%) of AD comorbidities, followed by arteriolosclerosis (up to 37%), and large-vessel atherosclerosis (up to 20%). Differences between the 3 groups included earlier age of onset in the American PSEN1 cases, shorter disease duration in sporadic cases, and more frequent large-vessel atherosclerosis and cerebral amyloid angiopathy in the Colombian PSEN1 cases. Logistic regression models adjusted for age and sex found the presence of a PSEN1 mutation, an apolipoprotein ε4 allele and TDP-43 pathology to predict an earlier age of onset; Hispanic ethnicity and multiracial subjects were predictive of severe CAA. Comorbidities are common in early onset AD and should be considered when planning clinical trials with such subjects. However, they may be at least partially dependent on ADNC and thus potentially addressable by anti-amyloid or and/anti-tau therapies.
This Letter presents the first measurements of the groomed jet radius Rg and the jet girth g in events with an isolated photon recoiling against a jet in lead-lead (PbPb) and proton-proton (pp) collisions at the LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The observables Rg and g provide a quantitative measure of how narrow or broad a jet is. The analysis uses PbPb and pp data samples with integrated luminosities of 1.7 nb−1 and 301 pb−1, respectively, collected with the CMS experiment in 2018 and 2017. Events are required to have a photon with transverse momentum pTγ>100 GeV and at least one jet back-to-back in azimuth with respect to the photon and with transverse momentum pTjet such that pTjet/pTγ>0.4. The measured Rg and g distributions are unfolded to the particle level, which facilitates the comparison between the PbPb and pp results and with theoretical predictions. It is found that jets with pTjet/pTγ>0.8, i.e., those that closely balance the photon pTγ, are narrower in PbPb than in pp collisions. Relaxing the selection to include jets with pTjet/pTγ>0.4 reduces the narrowing of the angular structure of jets in PbPb relative to the pp reference. This shows that selection bias effects associated with jet energy loss play an important role in the interpretation of jet substructure measurements.
The Higgs boson (H) trilinear self-coupling, λ3, is constrained via its measured properties and limits on the HH pair production using the proton-proton collision data collected by the CMS experiment at s=13TeV. The combination of event categories enriched in single-H and HH events is used to measure κλ, defined as the value of λ3 normalized to its standard model prediction, while simultaneously constraining the Higgs boson couplings to fermions and vector bosons. Values of κλ outside the interval −1.2<κλ<7.5 are excluded at 2σ confidence level, which is compatible with the expected range of −2.0<κλ<7.7 under the assumption that all other Higgs boson couplings are equal to their standard model predicted values. Relaxing the assumption on the Higgs couplings to fermions and vector bosons the observed (expected) κλ interval is constrained to be within −1.4<κλ<7.8 (−2.3<κλ<7.8) at 2σ confidence level.
Measurements at s=13.6TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8fb−1. Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavor and charge of the leptons, the number of jets, and number of jets originating from b quarks. The overall sensitivity is significantly better than that of previous results with a similar integrated luminosity. The improvement comes from a more refined control of experimental uncertainties and an improved fit strategy. An inclusive W+W− production cross section of 125.7±5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For the first time in proton-proton collisions, WW events with zero, one, and at least two jets are studied simultaneously and compared with recent theoretical predictions.
Oxygen consumption by oceanic microbes can predict respiration (CO2 production) but requires an assumed respiratory quotient (RQ; ΔO2/ΔCO2). Measured apparent RQs (ARQs) can be impacted by various processes, including nitrification and changes in dissolved organic matter (DOM) composition, leading to discrepancies between ARQ and actual RQ. In DOM remineralization experiments conducted in the eastern North Atlantic Ocean, ARQs averaged 1.39 ± 0.14, similar to predictions for complete consumption of plankton biomass. DOM removed with an elevated nominal oxidation state (i.e., more oxidized DOM), as detected by liquid chromatography-tandem mass spectrometry, coincided with increased hydrolyzable amino acid removal, increased ARQs and bacterioplankton respiration (BR), and a decreased bacterioplankton growth efficiency (BGE). Across experiments, evidence emerged that nitrification and DOM partial oxidation, driven in part by bacterioplankton members of OM43, SAR92 and Rhodobacteraceae, can elevate BR relative to bacterioplankton consumption of plankton-derived carbon. These rare synoptic measurements of interrelated variables reveal complex biochemical and cellular processes underlying variability in large-scale CO2 production estimates.
The animal gut microbiome is a complex system of diverse, predominantly anaerobic microbiota with secondary metabolite potential. These metabolites likely play roles in shaping microbial community membership and influencing animal host health. As such, novel secondary metabolites from gut microbes hold significant biotechnological and therapeutic interest. Despite their potential, gut microbes are largely untapped for secondary metabolites, with gut fungi and obligate anaerobes being particularly under-explored. To advance understanding of these metabolites, culture-based and (meta)genome-based approaches are essential. Culture-based approaches enable isolation, cultivation, and direct study of gut microbes, and (meta)genome-based approaches utilize in silico tools to mine biosynthetic gene clusters (BGCs) from microbes that have not yet been successfully cultured. In this mini-review, we highlight recent innovations in this area, including anaerobic biofoundries like ExFAB, the NSF BioFoundry for Extreme & Exceptional Fungi, Archaea, and Bacteria. These facilities enable high-throughput workflows to study oxygen-sensitive microbes and biosynthetic machinery. Such recent advances promise to improve our understanding of the gut microbiome and its secondary metabolism. KEY POINTS: • Gut microbial secondary metabolites have therapeutic and biotechnological potential • Culture- and (meta)genome-based workflows drive gut anaerobe metabolite discovery • Anaerobic biofoundries enable high-throughput workflows for metabolite discovery.
