Study protocol of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA).

Background and purpose:

Neuro­cog­nitive aging and the associated brain diseases impose a major social and economic burden. Therefore, substantial efforts have been put into revealing the lifestyle, the neurobiological and the genetic underpinnings of healthy neurocognitive aging. However, these studies take place almost exclusively in a limited number of highly-developed countries. Thus, it is an important open question to what extent their findings may generalize to neurocognitive aging in other, not yet investigated regions. The purpose of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA) is to collect multi-modal longitudinal data on healthy neurocognitive aging to address the data gap in this field in Central and Eastern Europe.

We adapted the Australian Ima­ging, Biomarkers and Lifestyle (AIBL) study of aging study protocol to local circumstances and collected demographic, lifestyle, men­tal and physical health, medication and medical history related information as well as re­cor­ded a series of magnetic resonance imaging (MRI) data. In addition, participants were al­so offered to participate in the collection of blood samples to assess circulating in­flam­matory biomarkers as well as a sleep study aimed at evaluating the general sleep quality based on multi-day collection of subjective sleep questionnaires and whole-night elec­troencephalographic (EEG) data.

Baseline data collection has al­ready been accomplished for more than a hundred participants and data collection in the se­cond
session is on the way. The collected data might reveal specific local trends or could also indicate the generalizability of previous findings. Moreover, as the HuBA protocol al­so offers a sleep study designed for tho­rough characterization of participants’ sleep quality and related factors, our extended multi-modal dataset might provide a base for incorporating these measures into healthy and clinical aging research. 

Besides its straightforward na­tional benefits in terms of health ex­pen­di­ture, we hope that this Hungarian initiative could provide results valid for the whole Cent­ral and Eastern European region and could also promote aging and Alzheimer’s disease research in these countries.

Formation of giant iron oxide-copper-gold deposits by superimposed episodic hydrothermal pulses.

Iron oxide-copper-gold (IOCG) deposits are a globally important source of copper, gold and critical commodities. Despite their relevance, IOCG deposits remain an ill-defined clan, with a range of characteristics that has complicated development of the general genetic model. Here we focus on the Candelaria IOCG deposit in Chile and reveal that by using micro-textural and compositional variations in actinolite, a common alteration mineral found in many IOCG deposits, we can constrain the evolution of these systems. We demonstrate that Candelaria formed by the superposition of at least two pulses of mineralization with a late Cu-rich event overprinting and superimposed over an early, and probably higher temperature, iron oxide-apatite (IOA) mineralization event. These distinct pulses were likely caused by episodic injections of magmatic-hydrothermal fluids from crystallizing magmas at depth. Our data provide empirical evidence of grain-to-deposit scale compositional and potentially temperature changes in an IOCG system. The results support the use of actinolite chemistry as a novel approach to understand the formation of IOCG deposits and a potential tool for vectoring in exploration.

Changes in Serum N-Glycome for Risk Drinkers: A Comparison with Standard Markers for Alcohol Abuse in Men and Women.

Background and aim: Glycomic alterations serve as biomarker tools for different diseases. The present study aims to evaluate the diagnostic capability of serum N-glycosylation to identify alcohol risk drinking in comparison with standard markers. Methods: We included 1516 adult individuals (age range 18-91 years; 55.3% women), randomly selected from a general population. A total of 143 (21.0%) men and 50 (5.9%) women were classified as risk drinkers after quantification of daily alcohol consumption and the Alcohol Use Disorders Identification Test (AUDIT). Hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) was used for the quantification of 46 serum N-glycan peaks. Serum gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and red blood cell mean corpuscular volume (MCV) were measured by standard clinical laboratory methods. Results: Variations in serum N-glycome associated risk drinking were more prominent in men compared to women. A unique combination of N-glycan peaks selected by the selbal algorithm shows good discrimination between risk-drinkers and non-risk drinkers for men and women. Receiver operating characteristics (ROC) curves show accuracy for the diagnosis of risk drinking, which is comparable to that of the golden standards, GGT, MCV and CDT markers for men and women. Additionally, the inclusion of N-glycan peaks improves the diagnostic accuracy of the standard markers, although it remains relatively low, due to low sensitivity. For men, the area under the ROC curve using N-glycome data is 0.75, 0.76, and 0.77 when combined with GGT, MCV, and CDT, respectively. In women, the areas were 0.76, 0.73, and 0.73, respectively. Conclusion: Risk drinking is associated with significant variations in the serum N-glycome, which highlights its potential diagnostic utility.

Thermal evolution of Andean iron oxide-apatite (IOA) deposits as revealed by magnetite thermometry.

Magnetite is the main constituent of iron oxide-apatite (IOA) deposits, which are a globally important source of Fe and other elements such as P and REE, critical for modern technologies. Geochemical studies of magnetite from IOA deposits have provided key insights into the ore-forming processes and source of mineralizing fluids. However, to date, only qualitative estimations have been obtained for one of the key controlling physico-chemical parameters, i.e., the temperature of magnetite formation. Here we reconstruct the thermal evolution of Andean IOA deposits by using magnetite thermometry. Our study comprised a > 3000 point geochemical dataset of magnetite from several IOA deposits within the Early Cretaceous Chilean Iron Belt, as well as from the Pliocene El Laco IOA deposit in the Chilean Altiplano. Thermometry data reveal that the deposits formed under a wide range of temperatures, from purely magmatic (~ 1000 to 800 °C), to late magmatic or magmatic-hydrothermal (~ 800 to 600 °C), to purely hydrothermal (< 600 °C) conditions. Magnetite cooling trends are consistent with genetic models invoking a combined igneous and magmatic-hydrothermal origin that involve Fe-rich fluids sourced from intermediate silicate magmas. The data demonstrate the potential of magnetite thermometry to better constrain the thermal evolution of IOA systems worldwide, and help refine the geological models used to find new resources.

Oxidized sulfur-rich arc magmas formed porphyry Cu deposits by 1.88 Ga.

Most known porphyry Cu deposits formed in the Phanerozoic and are exclusively associated with moderately oxidized, sulfur-rich, hydrous arc-related magmas derived from partial melting of the asthenospheric mantle metasomatized by slab-derived fluids. Yet, whether similar metallogenic processes also operated in the Precambrian remains obscure. Here we address the issue by investigating the origin, fO2, and S contents of calc-alkaline plutonic rocks associated with the Haib porphyry Cu deposit in the Paleoproterozoic Richtersveld Magmatic Arc (southern Namibia), an interpreted mature island-arc setting. We show that the ca. 1886-1881 Ma ore-forming magmas, originated from a mantle-dominated source with minor crustal contributions, were relatively oxidized (1‒2 log units above the fayalite-magnetite-quartz redox buffer) and sulfur-rich. These results indicate that moderately oxidized, sulfur-rich arc magma associated with porphyry Cu mineralization already existed in the late Paleoproterozoic, probably as a result of recycling of sulfate-rich seawater or sediments from the subducted oceanic lithosphere at that time.

Structural Contributions to Autocatalysis and Asymmetric Amplification in the Soai Reaction.

Diisopropylzinc alkylation of pyrimidine aldehydes-the Soai reaction, with its astonishing attribute of amplifying asymmetric autocatalysis-occupies a unique position in organic chemistry and stands as an eminent challenge for mechanistic elucidation. A new paradigm of "mixed catalyst-substrate" experiments with pyrimidine and pyridine systems allows a disconnection of catalysis from autocatalysis, providing insights into the role played by reactant and alkoxide structure. The alkynyl substituent favorably tunes catalyst solubility, aggregation, and conformation while modulating substrate reactivity and selectivity. The alkyl groups and the heteroaromatic core play further complementary roles in catalyst aggregation and substrate binding. In the study of these structure-activity relationships, novel pyridine substrates demonstrating amplifying autocatalysis were identified. Comparison of three autocatalytic systems representing a continuum of nitrogen Lewis basicity strength suggests how the strength of N-Zn binding events is a predominant contributor toward the rate of autocatalytic progression.

N-Glycosylation Alteration of Serum and Salivary Immunoglobulin a Is a Possible Biomarker in Oral Mucositis.

BACKGROUND: Oral and enteral mucositis due to high-dose cytostatic treatment administered during autologous and allogeneic stem-cell transplantation increases mortality. Salivary secretory immunoglobulin A (sIgA) is a basic pillar of local immunity in the first line of defense. Altered salivary sialoglycoprotein carbohydrates are important in the pathologies in the oral cavity including inflammation, infection and neoplasia. Therefore, we assessed whether changes in the salivary and serum IgA glycosylation correlated with development and severity of oral mucositis. METHODS: Using capillary electrophoresis, comparative analysis of serum and salivary IgA total N-glycans was conducted in 8 patients with autologous peripheral stem-cell transplantation (APSCT) at four different stages of transplantation (day -3/-7, 0, +7, +14) and in 10 healthy controls. RESULTS: Fourteen out of the 31 structures identified in serum and 6 out of 38 in saliva showed significant changes upon transplantation compared with the control group. Only serum core fucosylated, sialylated bisecting biantennary glycan (FA2BG2S2) showed significant differences between any two stages of transplantation (day -3/-7 and day +14; p = 0.0279). CONCLUSION: Our results suggest that changes in the serum IgA total N-glycan profile could serve as a disease-specific biomarker in patients undergoing APSCT, while analysis of salivary IgA N-glycan reflects the effect of APSCT on local immunity.

N-glycomic Analysis of Z(IgA1) Partitioned Serum and Salivary Immunoglobulin A by Capillary Electrophoresis.

AIMS: Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions. BACKGROUND: Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes. Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks. While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva. OBJECTIVE: Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders. METHODS: Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions. RESULTS: Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group. Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva. CONCLUSION: The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.

Demystifying the asymmetry-amplifying, autocatalytic behaviour of the Soai reaction through structural, mechanistic and computational studies.

The Soai reaction has profoundly impacted chemists' perspective of autocatalysis, chiral symmetry breaking, absolute asymmetric synthesis and its role in the origin of biological homochirality. Here we describe the unprecedented observation of asymmetry-amplifying autocatalysis in the alkylation of 5-(trimethylsilylethynyl)pyridine-3-carbaldehyde using diisopropylzinc. Kinetic studies with a surrogate substrate and spectroscopic analysis of a series of zinc alkoxides that incorporate specific structural mutations reveal a 'pyridine-assisted cube escape'. The new tetrameric cluster functions as a catalyst that activates the substrate through a two-point binding mode and poises a coordinated diisopropylzinc moiety for alkyl group transfer. Transition-state models leading to both the homochiral and heterochiral products were validated by density functional theory calculations. Moreover, experimental and computational analysis of the heterochiral complex provides a definitive explanation for the nonlinear behaviour of this system. Our deconstruction of the Soai system reveals the structural logic for autocatalyst evolution, function and substrate compatibility-a central mechanistic aspect of this iconic transformation.

High-energy ionizing radiation-induced degradation of amodiaquine in dilute aqueous solution: radical reactions and kinetics.

The widely used antimalarial drug amodiaquine (AQ) contains a 7-Cl-quinoline unit, a substituted 4-aminophenol part connected through the amino group and a tertiary amine part. The 4-aminophenol unit can be easily oxidized through radical intermediates to iminoquinone. This reaction also takes place in vitro and in vivo enzymatic reactions. The reaction is expected to have an important role in degradation of AQ in surface waters and also during degradation in advanced oxidation processes. In this paper by means of radiation chemical techniques the one-electron oxidation and reduction of AQ were studied using transient kinetics, kinetics of AQ degradation, formation and decay of end-products of radical reactions. The hydroxyl radicals were shown to add both to the quinoline (∼ 38%) and aminophenol (∼ 50%) parts via formation of hydroxycyclohexadienyl radicals and by H-abstraction or by an electron removal from the tertiary amine part of the molecule (∼ 12%). The dihydroxycyclohexadienyl radical formed on the aminophenol part is suggested to transform to aminophenoxy radical. The hydrated electrons can also effectively contribute to AQ degradation. Chemical oxygen demand and total organic carbon content investigations were also made in order to characterize the ionizing radiation-induced oxidation and mineralization. In aerated 0.1 mmol dm-3 solution, at 2.5 kGy absorbed dose AQ and its higher molecular mass degradation products demolished completely. Ionizing irradiation is a capable technique for degradation of AQ under both oxidative and reductive circumstances.

Inverted Binding of Non-natural Substrates in Strictosidine Synthase Leads to a Switch of Stereochemical Outcome in Enzyme-Catalyzed Pictet-Spengler Reactions.

The Pictet-Spengler reaction is a valuable route to 1,2,3,4-tetrahydro-ß-carboline (THBC) and isoquinoline scaffolds found in many important pharmaceuticals. Strictosidine synthase (STR) catalyzes the Pictet-Spengler condensation of tryptamine and the aldehyde secologanin to give (S)-strictosidine as a key intermediate in indole alkaloid biosynthesis. STRs also accept short-chain aliphatic aldehydes to give enantioenriched alkaloid products with up to 99% ee STRs are thus valuable asymmetric organocatalysts for applications in organic synthesis. The STR catalysis of reactions of small aldehydes gives an unexpected switch in stereopreference, leading to formation of the (R)-products. Here we report a rationale for the formation of the (R)-configured products by the STR enzyme from Ophiorrhiza pumila (OpSTR) using a combination of X-ray crystallography, mutational, and molecular dynamics (MD) studies. We discovered that short-chain aldehydes bind in an inverted fashion compared to secologanin leading to the inverted stereopreference for the observed (R)-product in those cases. The study demonstrates that the same catalyst can have two different productive binding modes for one substrate but give different absolute configuration of the products by binding the aldehyde substrate differently. These results will guide future engineering of STRs and related enzymes for biocatalytic applications.

Effects of Exercise on EEG Activity and Standard Tools Used to Assess Concussion.

A variety of cognitive assessment tools are used to determine the functional status of the brain before and after injury in athletes. Questionnaires, neuropsychological tests, and electroencephalographic (EEG) measures have been recently used to directly assess brain function on and near the playing field. However, exercise can affect cognitive performance and EEG measures of cortical activity. To date, little empirical evidence exists on the effects of acute exercise on these measures of neurological function. We therefore quantified athlete performance on a standardized battery of concussion assessment tools and EEG measurements immediately before and after acute exercise to simulate conditions of athletic competition. Heart rate and arterial oxygen levels were collected before and after the exercise challenge consisting of a 1-mile run. Together these data, from a gender-balanced cohort of collegiate athletes, demonstrated that moderate to hard levels of acute exercise improved performance on the King-Devick test (K-D test) and Standardized Assessment of Concussion (SAC) component of the Sport Concussion Assessment Tool (SCAT3). Gender played an important role in these effects, and performance was most affected by exercise in female athletes. EEG activity in the theta band (4-8 Hz) was decreased during periods of quiet resting with eyes open or eyes closed. Additionally, exercise produced a slowing of the EEG during the K-D test and a shift to higher frequencies during the balance assessment of the SCAT3. Together, these data indicate that exercise alone can influence outcome measures of cognitive assessment tools used to assess brain function in athletes. Finally, care must be taken to acquire postinjury measurements during a comparable physiologic state to that in which baseline assessment data were measured, and further research is needed into the factors influencing outcome measures of these tests.

Proteomics alterations in chicken jejunum caused by 24 h fasting.

The small intestine is the longest part of the chicken (Gallus gallus) gastrointestinal system that is specialized for nutrient absorption. It is known that decrease in intestinal villi area or height in early age can cause a reduction in essential nutrient intake, which may lead to delayed growth and consequently poorer performance of broiler chickens. The small intestinal absorptive surface is known to be affected by various factors, among others things the nutritional state. In our experiment, we aimed to investigate the possible protein expression alterations that lie behind the villus area and height decrease caused by feed deprivation. A total of 24 chickens were divided into three groups, namely ad libitum fed, fasted for 24 h, fasted for 24 h then refed for 2 h. The morphometric parameters were also measured in the duodenum, jejunum and ileum tissue sections using image analysis. Differential proteome analyses from jejunum samples were performed using two-dimensional difference gel electrophoresis followed by tryptic digestion and protein identification by matrix-assisted laser desorption/ionization mass spectrometry. Overall 541 protein spots were detected after 2D. Among them, eleven showed 1.5-fold or higher significant difference in expression and were successfully identified. In response to 24 h fasting, the expression of nine proteins was higher and that of two proteins was lower compared to the ad libitum fed group. The functions of the differentially expressed proteins indicate that the 24 h fasting mainly affects the expression of structural proteins, and proteins involved in lipid transport, general stress response, and intestinal defense.

Accumulation of magnetite by flotation on bubbles during decompression of silicate magma.

Magnetite (Fe3O4) is an iron ore mineral that is globally mined especially for steel production. It is denser (5.15 g/cm3) than Earth's crust (~2.7 g/cm3) and is expected to accumulate at the bottom of melt-rich magma reservoirs. However, recent studies revealed heterogeneous fluid bubble nucleation on oxide minerals such as magnetite during fluid degassing in volcanic systems. To test if the attachment on fluid bubbles is strong enough to efficiently float magnetite in silicate magma, decompression experiments were conducted at geologically relevant magmatic conditions with subsequent annealing to simulate re-equilibration after decompression. The results demonstrate that magnetite-bubble pairs do ascend in silicate melt, accumulating in an upper layer that grows during re-equilibration. This outcome contradicts the paradigm that magnetite must settle gravitationally in silicate melt.

Catalytic Enantioselective Hetero-[6+4] and -[6+2] Cycloadditions for the Construction of Condensed Polycyclic Pyrroles, Imidazoles, and Pyrazoles.

The development of the first chemo-, regio-, and stereoselective hetero-[6+4] and -[6+2] cycloadditions of heteroaromatic compounds via amino aza- and diazafulvenes is presented. Pyrroles, imidazoles, and pyrazoles substituted with a formyl group react with an aminocatalyst to generate an electron-rich hetero-6π-component that reacts in a chemo-, regio-, and stereoselective manner with electron-deficient dienes and olefins. For the hetero-[6+4] cycloaddition of the pyrrole system with dienes, a wide variation of both reaction partners is possible, providing attractive pyrrolo-azepine products in high yields and excellent enantioselectivities (99% ee). The hetero-[6+4] cycloaddition reaction concept is extended to include imidazoles and pyrazoles, giving imidazolo- and pyrazolo-azepines. The same activation concept is successfully employed to include hetero-[6+2] cycloadditions of the pyrrole system with nitroolefins, giving important pyrrolizidine-alkaloid scaffolds. Experimental NMR and mechanistic studies allowed for the identification of two different types of intermediates in the reaction. The first intermediate is the result of a rapid formation of an iminium ion, which generates a hetero-6π aminofulvene intermediate as a mixture of two isomers. Density functional theory calculations were used to determine the mechanism and sources of asymmetric induction in the hetero-[6+4] and -[6+2] cycloadditions. After formation of the reactive hetero-6π-components, a stepwise addition occurs with the diene or olefin, leading to a zwitterionic intermediate that undergoes cyclization to afford the cycloadduct, followed by eliminative catalyst release. The stereoselectivity is controlled by the second step, and computations elaborate on the various substrate and catalyst effects that alter the experimentally observed enantioselectivities. The computational studies provided a basis for improving the enantioselectivity of the hetero-[6+2] cycloaddition.

Formation of massive iron deposits linked to explosive volcanic eruptions.

The genetic link between magmas and ore deposit formation is well documented by studies of fossil hydrothermal systems associated with magmatic intrusions at depth. However, the role of explosive volcanic processes as active agents of mineralization remains unexplored owing to the fact that metals and volatiles are released into the atmosphere during the eruption of arc volcanoes. Here, we draw on observations of the uniquely preserved El Laco iron deposit in the Central Andes to shed new light on the metallogenic role of explosive volcanism that operates on a global scale. The massive magnetite (Fe3O4) ore bodies at El Laco have surface structures remarkably similar to basaltic lava flows, stimulating controversy about their origin. A long-standing debate has endured because all proposed models were constructed based exclusively on samples collected from surface outcrops representing the uppermost and most altered portion of the deposit. We overcome this sampling bias by studying samples retrieved from several drill cores and surface outcrops. Our results reveal complex lithological, textural and geochemical variations characterized by magmatic-like features and, most notably, a systematic increase in titanium concentration of magnetite with depth that account for an evolving system transitioning from purely magmatic to magmatic-hydrothermal conditions. We conclude that El Laco, and similar deposits worldwide, formed by a synergistic combination of common magmatic processes enhanced during the evolution of caldera-related explosive volcanic systems.

Organocatalytic [6+4] Cycloadditions via Zwitterionic Intermediates: Chemo-, Regio-, and Stereoselectivities.

The mechanisms and origins of chemo- and stereoselectivities of the organocatalytic [6+4] cycloaddition between 2-cyclopentenone and tropone have been investigated by a combined computational and experimental study. In the presence of a cinchona alkaloid primary amine catalyst and an acid additive, 2-cyclopentenone forms a cross-dienamine intermediate that subsequently undergoes a stepwise [6+4] cycloaddition reaction via a zwitterionic intermediate. The rate-determining transition state features a strong hydrogen-bonding interaction between the tropone oxygen atom and the protonated quinuclidine directing the reaction course leading to a highly periselective [6+4] cycloaddition. The importance of the strong hydrogen-bonding interaction is also demonstrated by the influence of the concentration of the acid additive on the yields and enantioselectivities of the reaction. The corresponding [4+2] cycloaddition reaction has a much higher energy barrier. The enantioselectivity of the [6+4] cycloaddition originates from different repulsive hydrogen-hydrogen interactions that distinguish the diastereomeric transition states.

Feeding state and age dependent changes in melanin-concentrating hormone expression in the hypothalamus of broiler chickens.

We aimed to quantify the gene expression changes of the potent orexigenic melanin-concentrating hormone (MCH) in chicken (Gallus gallus) hypothalamus with quantitative real-time polymerase chain reaction (qPCR), and for the first time determine peptide concentrations with a novel radioimmunoassay (RIA) under different feeding status. Three different experimental conditions, namely ad libitum feeding; fasting for 24 h; fasting for 24 h and then refeeding for 2 h, were applied to study changes of the aforementioned target and its receptor (MCHR4) gene expression under different nutritional status. The relative changes of MCH and MCHR4 were also studied from 7 to 35 days of age. Expression of PMCH and MCHR4 along the gastrointestinal tract (GIT) was also investigated. We found that expression of both targets was significant in the hypothalamus, while only weak expression was detected along the GIT. Different nutritional states did not affect the PMCH and MCHR4 mRNA levels. However, fasting for 24 h had significantly increased the MCH-like immunoreactivity by 25.65%. Fasting for 24 h and then refeeding for 2 h had further significantly increased the MCH peptide concentration by 32.51%, as compared to the ad libitum state. A decreasing trend with age was observable for both, the PMCH and MCHR4 mRNA levels, and also for the MCH-like immunoreactivity. Correlation analysis did not result in a significant correlation between MCH peptide concentration and abdominal fat mass in ad libitum fed birds. In conclusion, MCH peptide concentration altered in response to 24 h fasting, which indicated that this peptide may take part in feed intake regulation of broiler chickens.

Arynes and Cyclic Alkynes as Synthetic Building Blocks for Stereodefined Quaternary Centers.

We report a facile method to synthesize stereodefined quaternary centers from reactions of arynes and related strained intermediates using ß-ketoester-derived substrates. The conversion of ß-ketoesters to chiral enamines is followed by reaction with in situ generated strained arynes or cyclic alkynes. Hydrolytic workup provides the arylated or alkenylated products in enantiomeric excesses as high as 96%. We also describe the one-pot conversion of a ß-ketoester substrate to the corresponding enantioenriched α-arylated product. Computations show how chirality is transferred from the N-bound chiral auxiliary to the final products. These are the first theoretical studies of aryne trapping by chiral nucleophiles to set new stereocenters. Our approach provides a solution to the challenging problem of stereoselective ß-ketoester arylation/alkenylation, with formation of a quaternary center.