Microbial carbon use efficiency promotes global soil carbon storage.

Soils store more carbon than other terrestrial ecosystems1,2. How soil organic carbon (SOC) forms and persists remains uncertain1,3, which makes it challenging to understand how it will respond to climatic change3,4. It has been suggested that soil microorganisms play an important role in SOC formation, preservation and loss5-7. Although microorganisms affect the accumulation and loss of soil organic matter through many pathways4,6,8-11, microbial carbon use efficiency (CUE) is an integrative metric that can capture the balance of these processes12,13. Although CUE has the potential to act as a predictor of variation in SOC storage, the role of CUE in SOC persistence remains unresolved7,14,15. Here we examine the relationship between CUE and the preservation of SOC, and interactions with climate, vegetation and edaphic properties, using a combination of global-scale datasets, a microbial-process explicit model, data assimilation, deep learning and meta-analysis. We find that CUE is at least four times as important as other evaluated factors, such as carbon input, decomposition or vertical transport, in determining SOC storage and its spatial variation across the globe. In addition, CUE shows a positive correlation with SOC content. Our findings point to microbial CUE as a major determinant of global SOC storage. Understanding the microbial processes underlying CUE and their environmental dependence may help the prediction of SOC feedback to a changing climate.

Structural insights into the multifunctionality of rabies virus P3 protein.

Viruses form extensive interfaces with host proteins to modulate the biology of the infected cell, frequently via multifunctional viral proteins. These proteins are conventionally considered as assemblies of independent functional modules, where the presence or absence of modules determines the overall composite phenotype. However, this model cannot account for functions observed in specific viral proteins. For example, rabies virus (RABV) P3 protein is a truncated form of the pathogenicity factor P protein, but displays a unique phenotype with functions not seen in longer isoforms, indicating that changes beyond the simple complement of functional modules define the functions of P3. Here, we report structural and cellular analyses of P3 derived from the pathogenic RABV strain Nishigahara (Nish) and an attenuated derivative strain (Ni-CE). We identify a network of intraprotomer interactions involving the globular C-terminal domain and intrinsically disordered regions (IDRs) of the N-terminal region that characterize the fully functional Nish P3 to fluctuate between open and closed states, whereas the defective Ni-CE P3 is predominantly open. This conformational difference appears to be due to the single mutation N226H in Ni-CE P3. We find that Nish P3, but not Ni-CE or N226H P3, undergoes liquid-liquid phase separation and this property correlates with the capacity of P3 to interact with different cellular membrane-less organelles, including those associated with immune evasion and pathogenesis. Our analyses propose that discrete functions of a critical multifunctional viral protein depend on the conformational arrangements of distant individual domains and IDRs, in addition to their independent functions.

Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). CONCLUSIONS: The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

Wind Shapes the Growth Strategies of Trees in a Tropical Forest.

In tropical forests, trees strategically balance growth patterns to optimise fitness amid multiple environmental stressors. Wind poses the primary risk to a tree's mechanical stability, prompting developments such as thicker trunks to withstand the bending forces. Therefore, a trade-off in resource allocation exists between diameter growth and vertical growth to compete for light. We explore this trade-off by measuring the relative wind mortality risk for 95 trees in a tropical forest in Panama and testing how it varies with tree size, species and wind exposure. Surprisingly, local wind exposure and tree size had minimal impact on wind mortality risk; instead, species wood density emerged as the crucial factor. Low wood density species exhibited a significantly greater wind mortality risk, suggesting a prioritisation of competition for light over biomechanical stability. Our study highlights the pivotal role of wind safety in shaping the life-history strategy of trees and structuring diverse tropical forests.

Tall Bornean forests experience higher canopy disturbance rates than those in the eastern Amazon or Guiana shield.

The future of tropical forests hinges on the balance between disturbance rates, which are expected to increase with climate change, and tree growth. Whereas tree growth is a slow process, disturbance events occur sporadically and tend to be short-lived. This difference challenges forest monitoring to achieve sufficient resolution to capture tree growth, while covering the necessary scale to characterize disturbance rates. Airborne LiDAR time series can address this challenge by measuring landscape scale changes in canopy height at 1 m resolution. In this study, we present a robust framework for analysing disturbance and recovery processes in LiDAR time series data. We apply this framework to 8000 ha of old-growth tropical forests over a 4-5-year time frame, comparing growth and disturbance rates between Borneo, the eastern Amazon and the Guiana shield. Our findings reveal that disturbance was balanced by growth in eastern Amazonia and the Guiana shield, resulting in a relatively stable mean canopy height. In contrast, tall Bornean forests experienced a decrease in canopy height due to numerous small-scale (<0.1 ha) disturbance events outweighing the gains due to growth. Within sites, we found that disturbance rates were weakly related to topography, but significantly increased with maximum canopy height. This could be because taller trees were particularly vulnerable to disturbance agents such as drought, wind and lightning. Consequently, we anticipate that tall forests, which contain substantial carbon stocks, will be disproportionately affected by the increasing severity of extreme weather events driven by climate change.

Molecular Basis of Functional Effects of Phosphorylation of the C-Terminal Domain of the Rabies Virus P Protein.

The rabies virus (RABV) phosphoprotein (P protein) is expressed as several isoforms, which differ in nucleocytoplasmic localization and microtubule (MT) association, mediated by several sequences, including nuclear localization (NLS) and export (NES) sequences. This appears to underpin a functional diversity enabling multiple functions in viral replication and modulation of host biology. Mechanisms regulating trafficking are poorly defined, but phosphorylation by protein kinase C (PKC) in the P protein C-terminal domain (PCTD) regulates nuclear trafficking, mediated by PCTD-localized NLS/NES sequences, indicating that phosphorylation contributes to functional diversity. The molecular mechanism underlying the effects of PKC, and potential roles in regulating other host-cell interactions are unresolved. Here, we assess effects of phosphorylation on the P3 isoform, which differs from longer isoforms through an ability to localize to the nucleus and associate with MTs, which are associated with antagonism of interferon (IFN) signaling. We find that phosphomimetic mutation of the PKC site S210 inhibits nuclear accumulation and MT association/bundling. Structural analysis indicated that phosphomimetic mutation induces no significant structural change to the NLS/NES but results in the side chain of N226 switching its interactions from E228, within the NES, to E210. Intriguingly, N226 is the sole substituted residue between the PCTD of the pathogenic IFN-resistant RABV strain Nishigahara and a derivative attenuated IFN-sensitive strain Ni-CE, inhibiting P3 nuclear localization and MT association. Thus, S210 phosphorylation appears to impact on N226/E228 to regulate P protein localization, with N226 mutation in Ni-CE mimicking a constitutively phosphorylated state resulting in IFN sensitivity and attenuation. IMPORTANCE Rabies virus P protein is a multifunctional protein with critical roles in replication and manipulation of host-cell processes, including subversion of immunity. This functional diversity involves interactions of several P protein isoforms with the cell nucleus and microtubules. Previous studies showed that phosphorylation of the P protein C-terminal domain (PCTD) at S210, near nuclear trafficking sequences, regulates nucleocytoplasmic localization, indicating key roles in functional diversity. The molecular mechanisms of this regulation have remained unknown. Here, we show that phosphomimetic mutation of S210 regulates nuclear localization and MT association. This regulation does not appear to result from disrupted PCTD structure, but rather from a switch of specific side chain interactions of N226. Intriguingly, N226 was previously implicated in P protein nuclear localization/MT association, immune evasion, and RABV pathogenesis, through undefined mechanisms. Our data indicate that the S210-N226 interface is a key regulator of virus-host interactions, which is significant for pathogenesis.

Lyssavirus P Protein Isoforms Diverge Significantly in Subcellular Interactions Underlying Mechanisms of Interferon Antagonism.

Viral hijacking of microtubule (MT)-dependent transport is well understood, but several viruses also express discrete MT-associated proteins (vMAPs), potentially to modulate MT-dependent processes in the host cell. Specific roles for vMAP-MT interactions include subversion of antiviral responses by P3, an isoform of the P protein of rabies virus (RABV; genus Lyssavirus), which mediates MT-dependent antagonism of interferon (IFN)-dependent signal transducers and activators of transcription 1 (STAT1) signaling. P3 also undergoes nucleocytoplasmic trafficking and inhibits STAT1-DNA binding, indicative of intranuclear roles in a multipronged antagonistic strategy. MT association/STAT1 antagonist functions of P3 correlate with pathogenesis, indicating potential as therapeutic targets. However, key questions remain, including whether other P protein isoforms interact with MTs, the relationship of these interactions with pathogenesis, and the extent of conservation of P3-MT interactions between diverse pathogenic lyssaviruses. Using super-resolution microscopy, live-cell imaging, and immune signaling analyses, we find that multiple P protein isoforms associate with MTs and that association correlates with pathogenesis. Furthermore, P3 proteins from different lyssaviruses exhibit variation in intracellular localization phenotypes that are associated with STAT1 antagonist function, whereby P3-MT association is conserved among lyssaviruses of phylogroup I but not phylogroup II, while nucleocytoplasmic localization varies between P3 proteins of the same phylogroup within both phylogroup I and II. Nevertheless, the divergent P3 proteins retain significant IFN antagonist function, indicative of adaptation to favor different inhibitory mechanisms, with MT interaction important to phylogroup I viruses. IMPORTANCE Lyssaviruses, including rabies virus, cause rabies, a progressive encephalomyelitis that is almost invariably fatal. There are no effective antivirals for symptomatic infection, and effective application of current vaccines is limited in areas of endemicity, such that rabies causes ~59,000 deaths per year. Viral subversion of host cell functions, including antiviral immunity, is critical to disease, and isoforms of the lyssavirus P protein are central to the virus-host interface underpinning immune evasion. Here, we show that specific cellular interactions of P protein isoforms involved in immune evasion vary significantly between different lyssaviruses, indicative of distinct strategies to evade immune responses. These findings highlight the diversity of the virus-host interface, an important consideration in the development of pan-lyssavirus therapeutic approaches.

Order effects in PTSD network analysis: important implications for diagnostic conceptualization, treatment refinement, and research.

BACKGROUND: For decades confirmatory factor analysis (CFA) has been the preeminent method to study the underlying structure of posttraumatic stress disorder (PTSD); however, methodological limitations of CFA have led to the emergence of other analytic approaches. In particular, network analysis has become a gold standard to investigate the structure and relationships between PTSD symptoms. A key methodological limitation, however, which has significant clinical implications, is the lack of data on the potential impact of item order effects on the conclusions reached through network analyses. METHODS: The current study, involving a large sample (N = 5055) of active duty army soldiers following deployment to Iraq, assessed the vulnerability of network analyses and prevalence rate to item order effects. This was done by comparing symptom networks of the DSM-IV PTSD checklist items to these same items distributed in random order. Half of the participants rated their symptoms on traditionally ordered items and half the participants rated the same items, but in random order and interspersed between items from other validated scales. Differences in prevalence rate and network composition were examined. RESULTS: The prevalence rate differed between the ordered and random item samples. Network analyses using the ordered survey closely replicated the conclusions reached in the existing network analyses literature. However, in the random item survey, network composition differed considerably. CONCLUSION: Order effects appear to have a significant impact on conclusions reached from PTSD network analysis. Prevalence rates were also impacted by order effects. These findings have important diagnostic and clinical treatment implications.

Feasibility and Safety of Contrast-Enhanced Ultrasound of the Neonatal Brain: A Prospective Study Using MRI as the Reference Standard.

BACKGROUND. MRI is the reference standard for neonatal brain imaging, but it is expensive, time-consuming, potentially limited by availability and accessibility, and contraindicated in some patients. Transfontanelle neonatal head ultrasound is an excellent alternative but may be less sensitive and specific than MRI. Contrast-enhanced ultrasound (CEUS) has the potential to improve the capabilities of ultrasound. OBJECTIVE. The purpose of this study is to prospectively evaluate the feasibility, safety, and diagnostic performance of transfontanelle neonatal brain CEUS, with MRI used as the reference standard. METHODS. Neonates in the institutional neonatal ICU who were undergoing MRI as part of their clinical care were prospectively recruited to undergo portable brain ultrasound and CEUS for research purposes. Brain ultrasound and CEUS were performed portably without moving the patient from the isolette or crib in the neonatal ICU. Adverse events were recorded. Two radiologists independently evaluated ultrasound and CEUS images for abnormalities and then reached consensus regarding discrepancies. A separate radiologist reviewed MRI examinations. Sensitivity, specificity, and interreader agreement were evaluated, with MRI used as the reference. Qualitative post hoc image review was performed. RESULTS. Twenty-six neonates (nine boys and 17 girls; mean [± SD] age, 15.2 ± 14.0 days) were included. No significant alteration in patient vital signs or adverse reaction to the ultrasound contrast agent (UCA) occurred. The mean duration of the examination was significantly shorter for combined ultrasound and CEUS than for MRI (21.1 ± 4.7 vs 74.2 ± 34.8 minutes; p < .001). Interrater agreement for any abnormality was almost perfect for both ultrasound and CEUS (κ = 0.92 and 0.85, respectively). Sensitivity for any abnormality was 86.7% for ultrasound and 93.3% for CEUS; specificity was 100.0% for both. CEUS had sensitivity of 87.5% for acute or subacute ischemia and 100.0% for chronic ischemia; its specificity was 100.0% for acute or subacute ischemia and chronic ischemia. For both ultrasound and CEUS, sensitivity for subdural and intraparenchymal hemorrhage was poor (22.2-50.0%). On CEUS but not on MRI, post hoc review showed a case of postischemic hyperperfusion, which was confirmed by subsequently performed contrast-enhanced CT. CONCLUSION. The use of portable brain CEUS in neonates is feasible, safe, and more rapid than MRI. CLINICAL IMPACT. The potential diagnostic utility of brain neonatal CEUS relative to conventional ultrasound, particularly for ischemia, warrants further investigation.

Utility of Postnatal Chest X-Ray in Newborns for the Evaluation of Prenatally Suspected Congenital Pulmonary Airway Malformation: A Single-Center Experience.

OBJECTIVE: The aim of the study is to assess the necessity of chest X-ray (CXR) during the newborn hospitalization for all patients with prenatally suspected congenital pulmonary airway malformation (CPAM). STUDY DESIGN: This is a retrospective chart review of all infants delivered with prenatally suspected CPAM at our high-risk delivery hospital from January 2013 through April 2020 (n = 44). Nonparametric tests assessed the association between postnatal CXR findings, prescribed follow-up timeline, and neonatal outcomes. RESULTS: Mean follow-up period recommended was 6.4 weeks regardless of CXR findings in the neonatal period (p = 0.81). Additionally, patients who required respiratory support at or after birth were not more likely to have a lesion identified on chest X-ray (odds ratio [OR] = 0.72, 95% confidence interval [CI], 0.18-2.64, p = 0.71). CONCLUSION: Neonatal hospital course and future follow-up plan of patients with prenatally suspected CPAM were not altered by information from the CXR obtained in the immediate neonatal period, suggesting that this CXR may not be necessary in the asymptomatic patient. KEY POINTS: · Immediate postnatal X-ray of prenatally diagnosed CPAM does not alter planned follow-up interval.. · Immediate postnatal X-ray does not alter surgical plan for CPAM.. · Postnatal X-ray is not absolutely required for asymptomatic newborns with CPAM..

Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium.

OBJECTIVE: This study was aimed to describe utilization of therapeutic hypothermia (TH) in neonates presenting with mild hypoxic-ischemic encephalopathy (HIE) and associated neurological injury on magnetic resonance imaging (MRI) scans in these infants. STUDY DESIGN: Neonates ≥ 36 weeks' gestation with mild HIE and available MRI scans were identified. Mild HIE status was assigned to hyper alert infants with an exaggerated response to arousal and mild HIE as the highest grade of encephalopathy recorded. MRI scans were dichotomized as "injury" versus "no injury." RESULTS: A total of 94.5% (257/272) neonates with mild HIE, referred for evaluation, received TH. MRI injury occurred in 38.2% (104/272) neonates and affected predominantly the white matter (49.0%, n = 51). Injury to the deep nuclear gray matter was identified in (10.1%) 20 infants, and to the cortex in 13.4% (n = 14 infants). In regression analyses (odds ratio [OR]; 95% confidence interval [CI]), history of fetal distress (OR = 0.52; 95% CI: 0.28-0.99) and delivery by caesarian section (OR = 0.54; 95% CI: 0.31-0.92) were associated with lower odds, whereas medical comorbidities during and after cooling were associated with higher odds of brain injury (OR = 2.31; 95% CI: 1.37-3.89). CONCLUSION: Majority of neonates with mild HIE referred for evaluation are being treated with TH. Odds of neurological injury are over two-fold higher in those with comorbidities during and after cooling. Brain injury predominantly involved the white matter. KEY POINTS: · Increasingly, neonates with mild HIE are being referred for consideration for hypothermia therapy.. · Drift in clinical practice shows growing number of neonates treated with hypothermia as having mild HIE.. · MRI data show that 38% of neonates with mild HIE have brain injury, predominantly in the white matter..

Nanoscale characterization of drug-induced microtubule filament dysfunction using super-resolution microscopy.

BACKGROUND: The integrity of microtubule filament networks is essential for the roles in diverse cellular functions, and disruption of its structure or dynamics has been explored as a therapeutic approach to tackle diseases such as cancer. Microtubule-interacting drugs, sometimes referred to as antimitotics, are used in cancer therapy to target and disrupt microtubules. However, due to associated side effects on healthy cells, there is a need to develop safer drug regimens that still retain clinical efficacy. Currently, many questions remain open regarding the extent of effects on cellular physiology of microtubule-interacting drugs at clinically relevant and low doses. Here, we use super-resolution microscopies (single-molecule localization and optical fluctuation based) to reveal the initial microtubule dysfunctions caused by nanomolar concentrations of colcemid. RESULTS: We identify previously undetected microtubule (MT) damage caused by clinically relevant doses of colcemid. Short exposure to 30-80 nM colcemid results in aberrant microtubule curvature, with a trend of increased curvature associated to increased doses, and curvatures greater than 2 rad/µm, a value associated with MT breakage. Microtubule fragmentation was detected upon treatment with ≥ 100 nM colcemid. Remarkably, lower doses (< 20 nM after 5 h) led to subtle but significant microtubule architecture remodelling characterized by increased curvature and suppression of microtubule dynamics. CONCLUSIONS: Our results support the emerging hypothesis that microtubule-interacting drugs induce non-mitotic effects in cells, and establish a multi-modal imaging assay for detecting and measuring nanoscale microtubule dysfunction. The sub-diffraction visualization of these less severe precursor perturbations compared to the established antimitotic effects of microtubule-interacting drugs offers potential for improved understanding and design of anticancer agents.

Acute and Chronic Placental Abnormalities in a Multicenter Cohort of Newborn Infants with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE. STUDY DESIGN: Infants born at ≥36 weeks of gestation (n = 500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system. RESULTS: Complete placental pathologic examination was available for 321 of 500 (64%) trial participants. Placental abnormalities were identified in 273 of 321 (85%) and were more common in infants ≥40 weeks of gestation (93% vs 81%, P = .01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (-15.9 vs -14.3, P = .049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs 38.0, P < .001) and greater rates of clinically diagnosed chorioamnionitis (25% vs 2%, P < .001) than those without acute abnormalities. CONCLUSIONS: Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02811263.

Responses of ichthyoplankton assemblages to the recent marine heatwave and previous climate fluctuations in several Northeast Pacific marine ecosystems.

The effects of climate warming on ecosystem dynamics are widespread throughout the world's oceans. In the Northeast Pacific, large-scale climate patterns such as the El Niño/Southern Oscillation and Pacific Decadal Oscillation, and recently unprecedented warm ocean conditions from 2014 to 2016, referred to as a marine heatwave (MHW), resulted in large-scale ecosystem changes. Larval fishes quickly respond to environmental variability and are sensitive indicators of ecosystem change. Categorizing ichthyoplankton dynamics across marine ecosystem in the Northeast Pacific can help elucidate the magnitude of assemblage shifts, and whether responses are synchronous or alternatively governed by local responses to regional oceanographic conditions. We analyzed time-series data of ichthyoplankton abundances from four ecoregions in the Northeast Pacific ranging from subarctic to subtropical: the Gulf of Alaska (1981-2017), British Columbia (2001-2017), Oregon (1998-2017), and the southern California Current (1981-2017). We assessed the impact of the recent (2014-2016) MHW and how ichthyoplankton assemblages responded to past major climate perturbations since 1981 in these ecosystems. Our results indicate that the MHW caused widespread changes in the ichthyoplankton fauna along the coast of the Northeast Pacific Ocean, but impacts differed between marine ecosystems. For example, abundances for most dominant taxa were at all-time lows since the beginning of sampling in the Gulf of Alaska and British Columbia, while in Oregon and the southern California Current species richness increased as did abundances of species associated with warmer waters. Lastly, species associated with cold waters also increased in abundances close to shore in southern California during the MHW, a pattern that was distinctly different from previous El Niño events. We also found several large-scale, synchronized ichthyoplankton assemblage composition shifts during past major climate events. Current climate projections suggest that MHWs will become more intense and thus our findings can help project future changes in larval dynamics, allowing for improved ecosystem management decisions.

Self-assembled, optically-active {naphthalene diimide}U{cucurbit[8]uril} ensembles in an aqueous environment.

Naphthalene diimides (NDIs) are shown to arrange spontaneously co-facially with cucurbit[8]uril (CB[8]) in an aqueous environment through purely non-covalent interactions. The resultant 2 : 2 supramolecular complex of NDI and CB[8] is highly fluorescent (>30 times more than the constituent NDIs) due to the formation of NDI-NDI excimers within the supramolecular complex.

Wavelength-Dependent Fluorescent Immunosensors via Incorporation of Polarity Indicators near the Binding Interface of Antibody Fragments.

Herein, we describe a fluorescent immunosensor designed by incorporating an unnatural amino acid fluorophore into the binding site of an EGFR-specific antibody fragment, resulting in quantifiable EGFR-dependent changes in peak fluorescence emission wavelength. To date, immunosensor design strategies have relied on binding-induced changes in fluorescence intensity that are prone to excitation source fluctuations and sample-dependent noise. In this study, we used a rational design approach to incorporate a polarity indicator (Anap) into specific positions of an anti-EGFR single chain antibody to generate an emission wavelength-dependent immunosensor. We found that when incorporated within the topological neighborhood of the antigen binding interface, the Anap emission wavelength is blue-shifted by EGFR-binding in a titratable manner, up to 20 nm, with nanomolar detection limits. This approach could be applicable to other antibody/antigen combinations for integration into a wide range of assay platforms (including homogeneous, solid-phase assay, or microfluidic assays) for one-step protein quantification.

The Zero-Sum Fallacy in Evidence Evaluation.

There are many instances, both in professional domains such as law, forensics, and medicine and in everyday life, in which an effect (e.g., a piece of evidence or event) has multiple possible causes. In three experiments, we demonstrated that individuals erroneously assume that evidence that is equally predicted by two competing hypotheses offers no support for either hypothesis. However, this assumption holds only in cases in which competing causes are mutually exclusive and exhaustive (i.e., exactly one cause is true). We argue that this reasoning error is due to a zero-sum perspective on evidence, wherein people assume that evidence that supports one causal hypothesis must disconfirm its competitor. Thus, evidence cannot give positive support to both competitors. Across three experiments ( N = 49, N = 193, N = 201), we demonstrated that this error is robust to intervention and generalizes across several different contexts. We also ruled out several alternative explanations of the bias.

Harnessing Brightness in Naphthalene Diimides.

The development of brightly emissive compounds is of great research and commercial interest, with established and emerging applications across chemistry, biology, physics, medicine and engineering. Among the many types of molecules available, naphthalene diimides have been widely used for both fundamental photophysical studies and in practical applications that utilise fluorescence as an information readout. The monomeric naphthalene diimide is weakly fluorescent, however through various methods of core-derivatisation, it can be developed to be highly fluorescent and further functionalised to add utility. In this review, we highlight recent advances made in naphthalene diimide chemistry that have led to development of molecules with improved optical properties, and the design strategies utilised to produce bright fluorescence emission as small molecules or in supramolecular architectures.

A Multifunctional, Charge-Neutral, Chiral Octahedral M12 L12 Cage.

A chiral, octahedral M12 L12 cage, which is charge neutral and contains an internal void of about 2000 Å3 , is reported. The cage was synthesised as an enantiopure complex by virtue of amino-acid-based dicarboxylate ligands, which assemble around copper paddlewheels at the vertices of the octahedron. The cage persists in solution with retention of the fluorescence properties of the parent acid. The solid-state structure contains large pores both within and between the cages, and displays permanent porosity for the sorption of gases with retention of crystallinity. Initial tests show some enantioselectivity of the cage towards guests in solution.