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We evaluated the diagnostic performance of the ß-d-glucan (BDG) test (Beijing Gold Mountain River Tech) in diagnosing invasive fungal disease (IFD) and its variations among patients with different risks. Patients ≥18 years old who underwent a serum BDG test (positive cutoff value >80 pg/ml) from April 2017 through May 2018 were collected consecutively. Patients were classified into three groups: group 1, patients with host factors as defined by the prior 2008 European Organization for Research and Treatment (EORTC) criteria; group 2, those with extended host factors in 2020 EORTC criteria; and group 3, those without any risk factor mentioned in the criteria. IFD was defined by 2020 EORTC criteria, but BDG was not considered. Diagnostic performance of the serum BDG test was measured by the area under the curve (AUC) of the receiver-operating characteristic curve. Among 469 patients, 15.4% (72/469) were diagnosed with IFD (48/191 [25.1%], 14/144 [9.7%], and 10/134 [7.5%] in groups 1, 2, and 3, respectively). The BDG assay showed fair performance (AUC 0.748 [95% CI: 0.688-0.810]). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 77.8%, 60.7%, 26.4%, and 93.8%, respectively. PPV was higher in group 1, and NPV was higher in group 3. Additionally, diagnostic odds ratios were 6.73, 2.88, and 5.92 in groups 1, 2, and 3. Immunosuppressant use, non-IFD/Candida colonization, and central venous catheter were associated with false positivity. Clinicians should cautiously interpret the BDG assay, considering the various diagnostic performances depending on the different levels of risk.

We evaluated the diagnostic performance of the serum ß-d-glucan test in patients with varying risks for invasive fungal diseases. The test showed acceptable performance, but its predictive values differed among risk groups, highlighting the need for tailored interpretation.

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Fungal infections can be challenging to diagnose in returning travellers due to their non-specific clinical manifestations and changing epidemiology. We present a case of progressive disseminated histoplasmosis in a returning traveller from Bangladesh. The patient had a progressive and prolonged respiratory illness necessitating mechanical ventilatory support. The clue to potential fungal aetiology was provided by serum fungal markers - 1-3-ß-D-glucan and Aspergillus galactomannan. Diagnosis was eventually made using panfungal PCR on bronchioalveolar lavage fluid.

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OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 107 CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- ß -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-ß-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS: CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.

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Short tandem repeat (STR) typing has been regularly used in paternity disputes and forensic human identification linked caseworks. Occasionally, forensic scientists come across aberrant allele patterns during STR typing because of mutations, genetic variations, and other abnormalities. The tri-allelic pattern of STR is rare, particularly, the case where this pattern exists at 4 loci. Here, we report the type II tri-allelic patterns observed at vWA, SE33, D8S1179, and D13S317 loci in the product of conception (POC) sample during the course of our regular paternity case investigation. The DNA extracted from the blood samples and tissue of POC were subjected to STR typing for autosomal and sex STR loci using the commercial QIAGEN's Investigator® IDplex Plus Kit and QIAGEN's Investigator® 24plex QS Kit. Capillary electrophoresis was carried out in 3500 and 3500xL Genetic Analyzer Applied Biosystems and genotyped using GeneMapper ID-X Software v1.5 and v1.6. In this case of paternity inclusion, the POC sample displayed type II tri-allelic patterns at vWA (16, 19, 20), SE33 (19, 28.2, 29.2), D13S317 (16, 19, 20), and D8S1179 (10, 13, 17) loci. In addition, the POC displayed an abnormal genotype with a heterozygous peak imbalance (type II-B) of (1:2) pattern at D3S1358, D21S11, and D16S539 loci, of (2:1) pattern at D1S1656, D12S391, D10S1248, D2S1338, D2S441, D18S317, FGA, CSF1PO, and D5S818 loci, and type II-C allelic pattern (one single peak with triplicate height) at D19S433 and DS7820 loci. Understanding of such anomalous genotypes improves the knowledge about tri-allelic pattern of CODIS loci and helps in the appropriate interpretation of the results in STR typing.

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BACKGROUND: Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities. RESULTS: Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in ß-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage. CONCLUSIONS: Two novel P. pastoris chassis hosts with impaired ß-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.

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PURPOSE: Beta-D-Glucan (BDG) testing has been suggested to support the diagnosis of candidemia and invasive candidiasis. The actual benefit in critically ill high-risk patients in intensive care units (ICU) has not been verified so far. METHODS: In ICU patients receiving empirical echinocandin treatment for suspected invasive candidiasis (IC), serial BDG testing using the Fujifilm Wako Beta-Glucan Test was performed, starting on the first day of echinocandin administration and every 24-48 h afterwards. Diagnostic accuracy was determined for single testing and serial testing strategies using a range of cut-off values. In addition, we compared the added value of these testing strategies when their results were introduced as additional predictors into a multivariable logistic regression model controlling for established risk factors of IC. RESULTS: A total of 174 ICU patients, forty-six of which (25.7%) classified as cases of IC, were included in our study. Initial BDG testing showed moderate sensitivity (74%, 95%CI 59-86%) and poor specificity (45%, 95% CI 36-54%) for IC which could hardly be improved by follow-up testing. While raw BDG values or test results obtained with very high thresholds improved the predictive performance of our multivariable logistic regression model for IC, neither single nor serial testing with the manufacturer-proposed low-level cut-off showed substantial benefit. CONCLUSIONS: In our study of critically ill intensive care patients at high risk for candidemia or invasive candidiasis, diagnostic accuracy of BDG testing was insufficient to inform treatment decisions. Improved classification was only achieved for cases with very high BDG values.

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Foraging decisions shape the structure of food webs. Therefore, a behavioural shift in a single species can potentially modify resource-flow dynamics of entire ecosystems. To examine this, we conducted a field experiment to assess foraging niche dynamics of semi-arboreal brown anole lizards in the presence/absence of predatory ground-dwelling curly-tailed lizards in a replicated set of island ecosystems. One year after experimental translocation, brown anoles exposed to these predators had drastically increased perch height and reduced consumption of marine-derived food resources. This foraging niche shift altered marine-to-terrestrial resource-flow dynamics and persisted in the diets of the first-generation offspring. Furthermore, female lizards that displayed more risk-taking behaviours consumed more marine prey on islands with predators present. Our results show how predator-driven rapid behavioural shifts can alter food-web connectivity between oceanic and terrestrial ecosystems and underscore the importance of studying behaviour-mediated niche shifts to understand ecosystem functioning in rapidly changing environments.

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Co-infections with invasive candidiasis have been reported to be overrepresented in severe COVID-19. This report presents an unusual case of chronic Candida meningitis following intensive care for COVID-19.

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Carbon isotope composition of tree-ring (δ13 CRing ) is a commonly used proxy for environmental change and ecophysiology. δ13 CRing reconstructions are based on a solid knowledge of isotope fractionations during formation of primary photosynthates (δ13 CP ), such as sucrose. However, δ13 CRing is not merely a record of δ13 CP . Isotope fractionation processes, which are not yet fully understood, modify δ13 CP during sucrose transport. We traced, how the environmental intra-seasonal δ13 CP signal changes from leaves to phloem, tree-ring and roots, for 7 year old Pinus sylvestris, using δ13 C analysis of individual carbohydrates, δ13 CRing laser ablation, leaf gas exchange and enzyme activity measurements. The intra-seasonal δ13 CP dynamics was clearly reflected by δ13 CRing , suggesting negligible impact of reserve use on δ13 CRing . However, δ13 CP became increasingly 13 C-enriched during down-stem transport, probably due to post-photosynthetic fractionations such as sink organ catabolism. In contrast, δ13 C of water-soluble carbohydrates, analysed for the same extracts, did not reflect the same isotope dynamics and fractionations as δ13 CP , but recorded intra-seasonal δ13 CP variability. The impact of environmental signals on δ13 CRing , and the 0.5 and 1.7‰ depletion in photosynthates compared ring organic matter and tree-ring cellulose, respectively, are useful pieces of information for studies exploiting δ13 CRing .

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The gold standard for diagnosing invasive candidiasis still relies on blood cultures, which are inefficient and time-consuming to analyze. We developed an in-house qPCR assay to identify the 5 major Candida species in 78 peripheral blood (PB) samples from ICU patients at risk of candidemia. Blood cultures and (1,3)-ß-D-glucan (BDG) testing were performed concurrently to evaluate the performance of the qPCR. The qPCR was positive for DNA samples from all 20 patients with proven candidemia (positive PB cultures), showing complete concordance with Candida species identification in blood cultures, except for detection of dual candidemia in 4 patients, which was missed by blood cultures. Additionally, the qPCR detected Candida species in six DNA samples from patients with positive central venous catheters blood (CB) but negative PB cultures. BDG values were similarly high in these six samples and the ones with proven candidemia, strongly suggesting the diagnosis of a true candidemia episode despite the negative PB cultures. Samples from patients neither infected nor colonized yielded negative results in both the qPCR and BDG testing. Our qPCR assay was at least as sensitive as blood cultures, but with a shorter turnaround time. Furthermore, negative results from the qPCR provided strong evidence for the absence of candidemia caused by the five major Candida species.

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Chronic wounds, among others, are mainly characterized by prolonged inflammation associated with the overproduction of reactive oxygen species and pro-inflammatory cytokines by immune cells. As a consequence, this phenomenon hinders or even precludes the regeneration process. It is known that biomaterials composed of biopolymers can significantly promote the process of wound healing and regeneration. The aim of this study was to establish whether curdlan-based biomaterials modified with hop compounds can be considered as promising candidates for the promotion of skin wound healing. The resultant biomaterials were subjected to an evaluation of their structural, physicochemical, and biological in vitro and in vivo properties. The conducted physicochemical analyses confirmed the incorporation of bioactive compounds (crude extract or xanthohumol) into the curdlan matrix. It was found that the curdlan-based biomaterials improved with low concentrations of hop compounds possessing satisfactory hydrophilicity, wettability, porosity, and absorption capacities. In vitro, tests showed that these biomaterials were non-cytotoxic, did not inhibit the proliferation of skin fibroblasts, and had the ability to inhibit the production of pro-inflammatory interleukin-6 by human macrophages stimulated with lipopolysaccharide. Moreover, in vivo studies showed that these biomaterials were biocompatible and could promote the regeneration process after injury (study on Danio rerio larvae model). Thus, it is worth emphasizing that this is the first paper demonstrating that a biomaterial based on a natural biopolymer (curdlan) improved with hop compounds may have biomedical potential, especially in the context of skin wound healing and regeneration.

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BACKGROUND & AIMS: On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host-pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier. METHODS: Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3-ß-D-glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease. RESULTS: Patients with cirrhosis Child-Pugh class (CPC)-B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2-25.2) compared to patients with cirrhosis CPC-A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon-gamma-induced protein). Mortality differed significantly between patients with positive versus negative BDG (log-rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8-26.3). DISCUSSION: We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in-depth knowledge about (fungal-)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host-pathogen interactions and potentially introduce points of application for therapeutic interventions.

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This study aimed to investigate occupational exposure to particulate dust, endotoxin, and (1-3)-ß-D-glucan among workers involved in various poultry farming activities. A total of 298 personal samples were collected from randomly selected individuals from exposure groups based on distinct poultry farming activities comprising broiler farms, rearing, laying, hatchery, and catching activities. Aside from the inhalable particulate dust concentration that was determined, filter extracts were also analyzed for (1-3)-ß-D-glucan and endotoxin using the endpoint Glucatell® and Limulus amoebocyte lysate (LAL) assays, respectively. Data were analyzed using STATA 12 and linear regression models developed. The mean (GM) dust particulate concentration was 11.04 mg/m3 (GSD = 3.87); 2298 endotoxin units (EU/m3) (GSD = 10.56) and 149 ng/m3 for (1-3)-ß-D-glucan (GSD = 4.62). A modest positive correlation was observed between log-transformed endotoxin and (1-3)-ß-D-glucan concentrations (Pearson r = 0.44, p < .001), whilst a moderate negative correlation was observed for inhalable dust particulate and (1-3)-ß-D-glucan (Pearson r = -0.33, p < .001). However, there was a very poor correlation between inhalable dust and endotoxin (Pearson r = -0.02, p < .001). In the regression models, exposure group based on the nature of farming activity explained 50% of the variability in dust particulate and glucan levels. For dust particulate, rearing activities were significant predictors of higher dust levels compared to hatchery work, while rearing, laying, broiler and catching activities were significant predictors of higher endotoxin or glucan levels. Furthermore, working in a small broiler was a significant determinant of elevated glucan exposures. Farms using automated laying activities had significantly higher particulate levels compared to those using manual laying activities. This study revealed that workers engaged in poultry farming activities were exposed to significantly high levels of inhalable particulate dust, endotoxin, and (1-3)-ß-D-glucan concentrations, posing an increased risk for adverse respiratory health effects in these farm workers.

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Radix Puerariae thomsonii, the root of the botanical family Fabaceae species Pueraria montana var. thomsonii (Benth.) MR Almeida, can be used as food or medicine. Polysaccharides are important active constituents of this root. A low molecular weight polysaccharide, RPP-2 having α-D-1,3-glucan as the main chain, was isolated and purified. RPP-2 could promote the growth of probiotics in-vitro. Therefore, the effects of RPP-2 on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) C57/BL6J mouse models were investigated. RPP-2 could reduce HFD-induced liver injury by reducing inflammation, glucose metabolism, and steatosis, thereby improving NAFLD. RPP-2 regulated the abundances of intestinal floral genera Flintibacter, Butyricicoccus, and Oscillibacter, and their metabolites Lipopolysaccharide (LPS), bile acids, and short-chain fatty acids (SCFAs), thereby improving inflammation, lipid metabolism, and energy metabolism signaling pathways. These results confirmed that RPP-2 play a prebiotic role by regulating intestinal flora and microbial metabolites, playing a multi-pathway and multi-target role in improving NAFLD.

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The sensitivity of the (1-3)-ß-D-glucan (BDG) diagnostic test for candidemia varies in different clinical settings, and its usefulness in early diagnosis of candidemia is suboptimal. We evaluated the sensitivity of the test for early candidemia prediction. All adult patients with culture-proven candidemia who underwent a serum Goldstream Fungus (1-3)-ß-D-Glucan Test within seven days prior to candidemia onset at a tertiary referral hospital between January 2017 and May 2021 were included. Any-positive BDG results within seven days prior to candidemia onset were obtained in 38 out of 93 (40.9%) patients. The positive rate increased when the test was performed near the day of candidemia onset (P=0.04) but reached only 52% on the day of candidemia onset. We observed no significant differences between BDG-positive and -negative groups in terms of underlying disease, risk factors for candidemia, clinical presentation, origin of candidemia, and 30-day mortality. Candida albicans was significantly associated with positive BDG results than with all-negative BDG results (P=0.04). The Goldstream BDG test is unreliable for candidemia prediction because of its low sensitivity. Negative BDG results in patients with a high risk of invasive candidiasis should be interpreted with caution.

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Invasive pulmonary aspergillosis (IPA) may be a rare cause of granulomatous pneumonia in horses. The mortality of IPA is almost 100%; direct diagnostic tools in horses are needed. Bronchoalveolar lavage fluid (BALF) and serum samples were collected from 18 horses, including individuals suffering from IPA (n = 1), equine asthma (EA, n = 12), and 5 healthy controls. Serum samples were collected from another 6 healthy controls. Samples of BALF (n = 18) were analyzed for Aspergillus spp. DNA, fungal galactomannan (GM), ferricrocin (Fc), triacetylfusarinin C (TafC), and gliotoxin (Gtx). Analysis of 24 serum samples for (1,3)-ß-D-glucan (BDG) and GM was performed. Median serum BDG levels were 131 pg/mL in controls and 1142 pg/mL in IPA. Similar trends were observed in BALF samples for GM (Area under the Curve (AUC) = 0.941) and DNA (AUC = 0.941). The fungal secondary metabolite Gtx was detected in IPA BALF and lung tissue samples (86 ng/mL and 2.17 ng/mg, AUC = 1).

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Economists have limited causal evidence on how families receiving unconditional income would spend those funds. We examine financial and time investments in infants among families living in poverty from a large-scale, multi-site randomized controlled study of monthly unconditional cash. We find increased spending on child-specific goods and mothers' early-learning activities with their infants. The marginal propensity to consume child-focused items from the cash transfer exceeded that from other income, consistent with the behavioral cues in the design. We find no statistically detectable offsets in household earnings or impacts on pre-registered outcomes related to expenditures, labor supply, childcare or subjective well-being.

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The Cytochrome P450 (CYP450) superfamily has been the subject of intense research for over six decades. Here the HU227 strain of E. coli, lacking the δ-aminolevulinic acid (δ-ALA) synthase gene, was employed, along with [5-13C] δ-ALA, in the heterologous expression of P450cam harboring a prosthetic group labeled with 13C at the four methine carbons (Cm) and pyrrole Cα positions. The product was utilized as a proof of principle strategy for defining and refining solution phase active site structure in cytochrome P450cam, providing proton-to-proton distances from 13CmH to protons on bound substrate or nearby amino acid residues, using short mixing time 2D or 3D NOESY-HMQC methods. The results reveal the interesting finding that 2D 13C-filtered NOESY-HMQC can be used to obtain distances between protons on labeled 13C to positions of protons nearby in the active site, confirming the utility of this NMR-based approach to probing active site structure under physiological conditions. Such 13C-heme-filtered NOE data complement X-ray crystallographic and T1-based NMR measurements; and, may also be of potentially significant utility in furnishing experimental distance constraints in validations of docking routines commonly employed for determining the relative affinities and binding orientations of drug candidates with CYP450s.

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BACKGROUND: Food polysaccharide 1,3-ß-d-glucan (OBG) has been shown to alleviate ulcerative colitis (UC) in a mouse model, but the underlying mechanisms remain unclear. Here, we aimed to investigate potential mechanisms involving interactions among gut microbiota, microbial metabolites and host metabolic function. RESULTS: OBG alleviated colonic inflammation, barrier dysfunction and intestinal concentrations of short-chain fatty acids in mice with UC. In addition, the relative abundance of Muribaculaceae, Alistipes, Erysipelatoclostridium and Blautia increased, whereas the abundance of Proteus, Lachnospiraceae and Ruminococcus decreased within the gut microbiota upon OBG treatment. Kyoto Encyclopedia of Genes and Genomes analyses showed that intestinal enzymes altered upon OBG treatment were mainly enriched in sub-pathways of amino acid biosynthesis. Metabolomics analyses showed that l-tryptophan, l-tyrosine, l-phenylalanine and l-alanine increased, which is consistent with the predictive metabolism of gut microbiota. Correlation analysis and interaction networks highlighted gut microbiota (especially Lactobacillus, Parabacteroides, Proteus and Blautia), metabolites (especially l-phenylalanine, l-tryptophan, l-tyrosine and acetic acid) and metabolism (phenylalanine, tyrosine and tryptophan biosynthesis) that may be key targets of OBG. CONCLUSION: OBG is beneficial to the gut microecological balance in mice with colitis, mainly becaue of its impact on the interactions between gut microbes and amino acids metabolism (especially tyrosine and tryptophan metabolism). © 2022 Society of Chemical Industry.

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This paper examines causal sibling spillover effects among students from different family backgrounds in elementary and middle school. Family backgrounds are captured by race, household structure, mothers' educational attainment, and school poverty. Exploiting discontinuities in school starting age created by North Carolina school-entry laws, we adopt a quasi-experimental approach and compare test scores of public school students whose older siblings were born shortly before and after the school-entry cutoff date. We find that individuals whose older siblings were born shortly after the school-entry cutoff date have significantly higher test scores in middle school, and that this positive spillover effect is particularly strong in disadvantaged families. We estimate that the spillover effect accounts for approximately one third of observed statistical associations in test scores between siblings, and the magnitude is much larger for disadvantaged families. Our results suggest that spillover effects from older to younger siblings may lead to greater divergence in academic outcomes and economic inequality between families.