Safety and Immune Responses Following Anti-PD-1 Monoclonal Antibody Infusions in Healthy Persons With Human Immunodeficiency Virus on Antiretroviral Therapy.

Background: T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4+ T cells expressing programmed cell death 1 (PD-1) are enriched for latent HIV, making antibody to PD-1 a potential strategy to target the latent reservoir. Methods: This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on antiretroviral therapy with CD4+ counts ≥350 cells/µL who received 2 infusions of cemiplimab versus placebo. The primary outcome was safety, defined as any grade 3 or higher adverse event (AE) or any immune-related AE (irAE). Changes in HIV-1-specific polyfunctional CD4+ and CD8+ T-cell responses were evaluated. Results: Five men were enrolled (median CD4+ count, 911 cells/µL; median age, 51 years); 2 received 1 dose of cemiplimab, 2 received 2 doses, and 1 received placebo. One participant had a probable irAE (thyroiditis, grade 2); another had a possible irAE (hepatitis, grade 3), both after a single low-dose (0.3 mg/kg) infusion. The Safety Monitoring Committee recommended no further enrollment or infusions. All 4 cemiplimab recipients were followed for 48 weeks. No other cemiplimab-related serious AEs, irAEs, or grade 3 or higher AEs occurred. One 2-dose recipient of cemiplimab had a 6.2-fold increase in polyfunctional, Gag-specific CD8+ T-cell frequency with supportive increases in plasma HIV RNA and decreases in total HIV DNA. Conclusions: One of 4 participants exhibited increased HIV-1-specific T-cell responses and transiently increased HIV-1 expression following 2 cemiplimab infusions. The occurrence of irAEs after a single, low dose may limit translating the promising therapeutic results of cemiplimab for cancer to immunotherapeutic and latency reversal strategies for HIV. Clinical Trials Registration. NCT03787095.

Injury prevention strategies at the 2019 FIFA Women's World Cup display a multifactorial approach and highlight subjective wellness measurements.

OBJECTIVE: To report the injury prevention programs utilised by top-level female footballers competing internationally. METHODS: An online survey was administered to physicians of the 24 competing national teams at the 2019 Federation Internationale de Football Association (FIFA) Women's World Cup. The survey included 4 sections regarding perceptions and practices concerning non-contact injuries: (1) risk factors, (2) screening tests and monitoring tools, (3) preventative strategies, and (4) reflection on their World Cup experience. RESULTS: Following responses from 54% of teams, the most common injuries encountered included muscle strains, ankle sprains, and anterior cruciate ligament ruptures. The study also revealed the most important injury risk factors during the FIFA 2019 World Cup. Intrinsic risk factors include accumulated fatigue, previous injury, and strength endurance. Extrinsic risk factors include reduced recovery time between matches, congested match schedule, and the number of club team matches played. The 5 most used tests for risk factors were flexibility, joint mobility, fitness, balance, and strength. Monitoring tools commonly used were subjective wellness, heart rate, minutes/matches played, and daily medical screening. Specific strategies to limit the risk of an anterior cruciate ligament injury included the FIFA 11+ program and proprioception training. CONCLUSION: The present study revealed multifactorial approaches to injury prevention strategies for women's national football teams at the FIFA 2019 World Cup. Challenges to injury prevention program implementation reflect time limitations, schedule uncertainties, and varying club team recommendations. LEVEL OF EVIDENCE: IV.

Evolution of milk oligosaccharides: Origin and selectivity of the ratio of milk oligosaccharides to lactose among mammals.

BACKGROUND: The carbohydrate fraction of mammalian milk is constituted of lactose and oligosaccharides, most of which contain a lactose unit at their reducing ends. Although lactose is the predominant saccharide in the milk of most eutherians, oligosaccharides significantly predominate over lactose in the milk of monotremes and marsupials. SCOPE OF REVIEW: This review describes the most likely process by which lactose and milk oligosaccharides were acquired during the evolution of mammals and the mechanisms by which these saccharides are digested and absorbed by the suckling neonates. MAJOR CONCLUSIONS: During the evolution of mammals, c-type lysozyme evolved to α-lactalbumin. This permitted the biosynthesis of lactose by modulating the substrate specificity of ß4galactosyltransferase 1, thus enabling the concomitant biosynthesis of milk oligosaccharides through the activities of several glycosyltransferases using lactose as an acceptor. In most eutherian mammals the digestion of lactose to glucose and galactose is achieved through the action of intestinal lactase (ß-galactosidase), which is located within the small intestinal brush border. This enzyme, however, is absent in neonatal monotremes and macropod marsupials. It has therefore been proposed that in these species the absorption of milk oligosaccharides is achieved by pinocytosis or endocytosis, after which digestion occurs through the actions of several lysosomal acid glycosidases. This process would enable the milk oligosaccharides of monotremes and marsupials to be utilized as a significant energy source for the suckling neonates. GENERAL SIGNIFICANCE: The evolution and significance of milk oligosaccharides is discussed in relation to the evolution of mammals.

Establishing Age- and Sex-Specific Norms for Pediatric Return-to-Sports Physical Performance Testing.

BACKGROUND: Graft tears and contralateral anterior cruciate ligament (ACL) tears are common in pediatric athletes after ACL reconstruction. Use of objective return-to-sports (RTS) criteria, in particular physical performance tests (PPTs), is believed to reduce the incidence of secondary injury; however, pediatric norms for these tests are unknown. PURPOSE: To establish a proof of concept for the creation of age- and sex-based norms for commonly used RTS PPTs in healthy pediatric athletes, allowing the creation of growth curves for clinical referencing. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 100 healthy people who were between the ages of 6 and 18 years and involved in organized sports were enrolled, with even distributions of age and sex. All participants underwent 9 common RTS PPTs: stork test, stork test on Bosu, single-leg squat, single-leg squat on Bosu, clockwise and counterclockwise quadrant hops, single-leg hop for distance, 6-m timed hop, and triple crossover hop for distance. Mean performance across limbs was calculated for each individual. Chronological age, height, weight, sex, and self-reported Pubertal Maturational Observational Scale (PMOS) score were recorded. Univariable and multivariable models were created for each PPT, assessing the importance of the recorded descriptive variables. Quantile regression was used to create growth curves for each PPT. RESULTS: The cohort was 52% female, and the mean ± standard deviation age was 11.7 ± 3.6 years. PMOS was highly correlated with age (r = 0.86) and was excluded from the regressions. In univariable regression, age, height, and weight were strong predictors of performance for all PPTs, whereas sex was a predictor of performance on the single-leg and triple crossover hops for distance (with males outperforming females). Height and weight were excluded from multivariable regression because of multicollinearity with age. Multivariable regression showed predictive patterns for age and sex that were identical to those shown in the univariable analysis. Given ceiling effects, quantile regression for the stork tests was not possible, but quantile regression growth curves were successfully created for the 7 remaining PPTs. CONCLUSION: Chronological age and sex accurately predicted performance on common RTS PPTs in pediatric patients. The growth curves presented herein could assist clinicians with benchmarking pediatric patients postoperatively against a healthy athletic cohort.

Healthy Pediatric Athletes Have Significant Baseline Limb Asymmetries on Common Return-to-Sport Physical Performance Tests.

BACKGROUND: Return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction in children is associated with a much higher risk (∼30%) of subsequent ACL injury than in adults. Most RTS testing protocols use a limb symmetry index (LSI) ≥90% on physical performance tests (PPTs) to assess an athlete's readiness for sport. This assumes that, in a healthy state, the physical performances across both lower extremities are and should be equal. PURPOSE: To determine the prevalence of limb asymmetries >10% in the uninjured pediatric population on common PPTs as well as to explore the relationship between athlete variables, limb preference, and LSI values. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This study included healthy volunteers (N = 100) evenly distributed between the ages of 6 and 18 years (mean age, 11.7 ± 3.6 years; 52% female). Participants performed 9 common PPTs. For analysis, we developed a composite score for each limb by averaging trials. We then calculated the LSI for each test. Univariable and multivariable linear regression analyses were performed to assess the relationship between athlete variables (age, sex, height, and weight) and LSI for each PPT. RESULTS: Instances of poor baseline limb symmetry (<90% LSI) were common across all PPTs. The single-leg timed hop had the highest percentage of participants, with LSI ≥90% at 73%, while the stork on a Bosu ball had the lowest percentage at 23%. After adjusting for age, female sex showed a significant association with LSI for the stork test (P = .010) and the quadrant hop-counterclockwise (P = .021). Additionally, after adjusting for sex, increasing age showed a significant association with LSI for the stork test (P < .001), single-leg squat on a Bosu ball (P = .010), quadrant hop-clockwise (P = .016), and quadrant hop-counterclockwise (P = .009). CONCLUSION: The majority of healthy athletes 18 years and younger demonstrated significant (<90%) limb asymmetries. Limb symmetry was not consistently affected by participant age or sex, and the effect sizes of these relationships were small. These findings should encourage clinicians and coaches to exercise caution in using the LSI as an isolated measure of RTS readiness after injury in pediatric athletes.

Development of Concise Physical Performance Test Batteries in Young Athletes.

PURPOSE: This study aimed 1) to define the principal components of physical function assessed by 10 common lower extremity physical performance tests and 2) to derive a reduced-item set of physical performance tests that efficiently and accurately measures raw performance and limb symmetry on each underlying component in pediatric and adolescent athletes. METHODS: This study included healthy, uninjured volunteers (n = 100) between the ages 6 and 18 yr (mean age = 11.7 ± 3.6 yr; 52 females). Subjects performed the stork balance, stork balance on BOSU® Balance Trainer, single leg squat (SLS), SLS on BOSU, clockwise and counterclockwise quadrant single leg hop (SLH), forward SLH, timed SLH, triple crossover SLH, and lower quarter Y-Balance Test™. Item reduction was performed using principal components analysis (PCA). We developed separate principal components analysis for average raw performance and side-to-side limb symmetry, with secondary analyses to evaluate consistency of results by age and sex. RESULTS: We identified two components for average raw performance (accounting for 65.2% of the variance in total test battery) with a reduced-item set composed of five tests, and four components for limb symmetry (accounting for 62.9% of the variance in total test battery) with a reduced-item set of seven tests. The most parsimonious test suitable for screening both average raw performance and limb symmetry would consist of five tests (stork balance on BOSU, SLS on BOSU, forward SLH, timed SLH, and lower quarter Y-Balance Test™). Age- and sex-specific test batteries may be warranted. CONCLUSION: Comprehensive screening for lower extremity average raw performance and limb symmetry is possible with short physical performance test batteries.

Quantum Simulation Meets Nonequilibrium Dynamical Mean-Field Theory: Exploring the Periodically Driven, Strongly Correlated Fermi-Hubbard Model.

We perform an ab initio comparison between nonequilibrium dynamical mean-field theory and optical lattice experiments by studying the time evolution of double occupations in the periodically driven Fermi-Hubbard model. For off-resonant driving, the range of validity of a description in terms of an effective static Hamiltonian is determined and its breakdown due to energy absorption close to resonance is demonstrated. For near-resonant driving, we investigate the response to a change in driving amplitude and discover an asymmetric excitation spectrum with respect to the detuning. In general, we find good agreement between experiment and theory, which cross validates the experimental and numerical approaches in a strongly correlated nonequilibrium system.

Floquet Dynamics in Driven Fermi-Hubbard Systems.

We study the dynamics and timescales of a periodically driven Fermi-Hubbard model in a three-dimensional hexagonal lattice. The evolution of the Floquet many-body state is analyzed by comparing it to an equivalent implementation in undriven systems. The dynamics of double occupancies for the near- and off-resonant driving regime indicate that the effective Hamiltonian picture is valid for several orders of magnitude in modulation time. Furthermore, we show that driving a hexagonal lattice compared to a simple cubic lattice allows us to modulate the system up to 1 s, corresponding to hundreds of tunneling times, with only minor atom loss. Here, driving at a frequency close to the interaction energy does not introduce resonant features to the atom loss.

Enhancement and sign change of magnetic correlations in a driven quantum many-body system.

Periodic driving can be used to control the properties of a many-body state coherently and to realize phases that are not accessible in static systems. For example, exposing materials to intense laser pulses makes it possible to induce metal-insulator transitions, to control magnetic order and to generate transient superconducting behaviour well above the static transition temperature. However, pinning down the mechanisms underlying these phenomena is often difficult because the response of a material to irradiation is governed by complex, many-body dynamics. For static systems, extensive calculations have been performed to explain phenomena such as high-temperature superconductivity. Theoretical analyses of driven many-body Hamiltonians are more challenging, but approaches have now been developed, motivated by recent observations. Here we report an experimental quantum simulation in a periodically modulated hexagonal lattice and show that antiferromagnetic correlations in a fermionic many-body system can be reduced, enhanced or even switched to ferromagnetic correlations (sign reversal). We demonstrate that the description of the many-body system using an effective Floquet-Hamiltonian with a renormalized tunnelling energy remains valid in the high-frequency regime by comparing the results to measurements in an equivalent static lattice. For near-resonant driving, the enhancement and sign reversal of correlations is explained by a microscopic model of the system in which the particle tunnelling and magnetic exchange energies can be controlled independently. In combination with the observed sufficiently long lifetimes of the correlations in this system, periodic driving thus provides an alternative way of investigating unconventional pairing in strongly correlated systems experimentally.

Ketamine Therapy for Treatment-resistant Depression in a Patient with Multiple Sclerosis: A Case Report.

Objective: Depression is a common condition among patients with multiple sclerosis and often becomes resistant to oral antidepressants. We report a patient with multiple sclerosis who developed severe treatment-resistant depression and who was successfully treated with intravenous ketamine over the period of two years. Methods: Ketamine treatment protocol included an initial series of six treatments administered every other day, followed by a maintenance schedule. Ketamine was administered intravenously at 0.5mg/kg of ideal body weight over 40 minutes. Depression symptoms were measured using Beck Depression Index. Results: The patient's Beck Depression Index score prior to initiating ketamine treatment was 38, corresponding to severe depression. Response to treatment, defined as 50-percent reduction in Beck Depression Index score, was observed after five treatments. For this patient, the maintenance schedule ranged from a weekly treatment to one treatment every three weeks. During the two-year observation period, this patient was able to maintain a stable non-depressed mood and had no worsening of her MS symptoms. Conclusion: Ketamine may be an alternative treatment for resistant depression and may have a special use in patients with multiple sclerosis.

Multi-scale detection of rate changes in spike trains with weak dependencies.

The statistical analysis of neuronal spike trains by models of point processes often relies on the assumption of constant process parameters. However, it is a well-known problem that the parameters of empirical spike trains can be highly variable, such as for example the firing rate. In order to test the null hypothesis of a constant rate and to estimate the change points, a Multiple Filter Test (MFT) and a corresponding algorithm (MFA) have been proposed that can be applied under the assumption of independent inter spike intervals (ISIs). As empirical spike trains often show weak dependencies in the correlation structure of ISIs, we extend the MFT here to point processes associated with short range dependencies. By specifically estimating serial dependencies in the test statistic, we show that the new MFT can be applied to a variety of empirical firing patterns, including positive and negative serial correlations as well as tonic and bursty firing. The new MFT is applied to a data set of empirical spike trains with serial correlations, and simulations show improved performance against methods that assume independence. In case of positive correlations, our new MFT is necessary to reduce the number of false positives, which can be highly enhanced when falsely assuming independence. For the frequent case of negative correlations, the new MFT shows an improved detection probability of change points and thus, also a higher potential of signal extraction from noisy spike trains.

Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption.

BACKGROUND: The discovery of potent and broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) has made passive immunization a potential strategy for the prevention and treatment of HIV infection. We sought to determine whether passive administration of VRC01, a bNAb targeting the HIV CD4-binding site, can safely prevent or delay plasma viral rebound after the discontinuation of antiretroviral therapy (ART). METHODS: We conducted two open-label trials (AIDS Clinical Trials Group [ACTG] A5340 and National Institutes of Health [NIH] 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART. RESULTS: A total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 µg per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P=0.04 by a two-sided Fisher's exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher's exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus. CONCLUSIONS: VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326 .).

Chemical characterization of milk oligosaccharides of the tiger quoll (Dasyurus maculatus), a marsupial.

Milk oligosaccharides were separated from the carbohydrate fraction of milk of the tiger quoll a species of marsupial that is closely related to the eastern quoll, Dasyurus viverrinus. They were characterized by (1)H - nuclear magnetic resonance spectroscopy and matrix - assisted laser desorption/ionization time-of-flight mass spectrometry. The following oligosaccharides were identified; Gal(ß1-3)Gal(ß1-4)Glc, Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Gal(ß1-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Neu5Ac(α2-3) Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc with an α(2-3)Neu5Ac linked to ß(1-4)Gal residue of either branch of Gal(ß1-4)GlcNAc(ß1-6) units, and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc with a ß(1-3) linked Gal and an α(2-3) linked Neu5Ac. In addition, larger oligosaccharides were characterized as follows; Gal(ß1-3){Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)GlcNAc(ß1-6)}Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3){Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)GlcNAc(ß1-6)}Gal(ß1-4)Glc and their α(2-3) linked Neu5Ac derivatives.

Chemical characterization of milk oligosaccharides of the common wombat (Vombatus ursinus).

Previous structural characterizations of marsupial milk oligosaccharides have been performed in the tammar wallaby, red kangaroo, koala, common brushtail possum and the eastern quoll. To clarify the homology and heterogeneity of milk oligosaccharides among marsupial species, which could provide information on their evolution, the oligosaccharides of wombat milk carbohydrate were characterized in this study. Neutral and acidic oligosaccharides were isolated from the carbohydrate fractions of two samples of milk of the common wombat and characterized by (1) H-nuclear magnetic resonance spectroscopy. The structures of six neutral saccharides were found to be Gal(ß1-4)Glc (lactose), Gal(ß1-3)Gal(ß1-4)Glc (3'-galactosyllactose), Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc (3',3"-digalactosyllactose), Gal(ß1-3)Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc, Gal(ß1-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (galactosyl lacto-N-novopentaose I) and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novooctaose), while those of six acidic saccharides were Neu5Ac(α2-3)Gal(ß1-3)Gal(ß1-4)Glc. (sialyl 3'-galactosyllactose), Neu5Ac(α2-3)Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc (sialyl 3',3"-digalactosyllactose), Neu5Ac(α2-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (sialyl lacto-N-novopentaose a), Gal(ß1-3)[Neu5Ac(α2-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (sialyl lacto-N-novopentaose c), Neu5Ac(α2-3)Gal(ß1-3)Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc,, Neu5Ac(α2-3)Gal(ß1-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc and Gal(ß1-3)Gal(ß1-3)[Neu5Ac(α2-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc. In addition, small amounts of sulfated oligosaccharides but no oligosaccharides containing Neu5Gc or α(2-6) linked Neu5Ac were detected.

Exploring competing density order in the ionic Hubbard model with ultracold fermions.

We realize and study the ionic Hubbard model using an interacting two-component gas of fermionic atoms loaded into an optical lattice. The bipartite lattice has a honeycomb geometry with a staggered energy offset that explicitly breaks the inversion symmetry. Distinct density-ordered phases are identified using noise correlation measurements of the atomic momentum distribution. For weak interactions the geometry induces a charge density wave. For strong repulsive interactions we detect a strong suppression of doubly occupied sites, as expected for a Mott insulating state, and the externally broken inversion symmetry is not visible anymore in the density distribution. The local density distributions in different configurations are characterized by measuring the number of doubly occupied lattice sites as a function of interaction and energy offset. We further probe the excitations of the system using direction dependent modulation spectroscopy and discover a complex spectrum, which we compare with a theoretical model.

Creating State-Dependent Lattices for Ultracold Fermions by Magnetic Gradient Modulation.

We demonstrate a versatile method for creating state-dependent optical lattices by applying a magnetic field gradient modulated in time. This allows for tuning the relative amplitude and sign of the tunneling for different internal states. We observe substantially different momentum distributions depending on the spin state of fermionic ^{40}K atoms. Using dipole oscillations, we probe the spin-dependent band structure and find good agreement with theory. In situ expansion dynamics demonstrate that one state can be completely localized while others remain itinerant. A systematic study shows negligible heating and lifetimes of several seconds in the Hubbard regime.

Chemical characterization of milk oligosaccharides of the eastern quoll (Dasyurus viverrinus).

Structural characterizations of marsupial milk oligosaccharides have been performed in four species to date: the tammar wallaby (Macropus eugenii), the red kangaroo (Macropus rufus), the koala (Phascolarctos cinereus) and the common brushtail possum (Trichosurus vulpecula). To clarify the homology and heterogeneity of milk oligosaccharides among marsupials, the oligosaccharides in the carbohydrate fraction of eastern quoll milk were characterized in this study. Neutral and acidic oligosaccharides were separated and characterized by (1)H-nuclear magnetic resonance spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The structures of the neutral oligosaccharides were Gal(ß1-3)Gal(ß1-4)Glc (3'-galactosyllactose), Gal(ß1-3)Gal(ß1-3)Gal(ß1-4)Glc (3",3'-digalactosyllactose), Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novopentaose I), Gal(ß1-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (galactosyl lacto-N-novopentaose I), Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)Gal(ß1-4)Glc (galactosyl lacto-N-novopentaose II), Gal(ß1-3)[Gal(ß1-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (galactosyl lacto-N-novopentaose III) and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novooctaose). The structures of the acidic oligosaccharides detected are Neu5Ac(α2-3)Gal(ß1-4)Glc (3'-sialyllactose), Gal(ß1-3)(O-3-sulfate)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novopentaose I sulfate a), Gal(ß1-3)[Gal(ß1-4)(O-3-sulfate)GlcNAc(ß1-6)]Gal(ß1-4)Glc (lacto-N-novopentaose I sulfate b), Neu5Ac(α2-3)Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (sialyl lacto-N-novopentaose a), Gal(ß1-3)[Neu5Ac(α2-3)Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc (sialyl lacto-N-novopentaose c), Neu5Ac(α2-3) Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc, and Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-3)[Gal(ß1-4)GlcNAc(ß1-6)]Gal(ß1-4)Glc with an α(2-3) Neu5Ac linked to ß(1-4)Gal residue of either branch of Gal(ß1-4)GlcNAc(ß1-6) units. The most predominant oligosaccharides in the carbohydrate fraction of mid-lactation milk were found to be lacto-N-novopentaose I and lacto-N-novooctaose, i.e., branched oligosaccharides that contain N-acetylglucosamine. The predominance of these branched oligosaccharides, rather than of a series of linear ß(1-3) linked galacto oligosaccharides, appears to be the main feature of the eastern quoll milk oligosaccharides that differentiates them from those of the tammar wallaby and the brushtail possum.

4-O-Acetyl-sialic acid (Neu4,5Ac2) in acidic milk oligosaccharides of the platypus (Ornithorhynchus anatinus) and its evolutionary significance.

Monotremes (echidnas and platypus) retain an ancestral form of reproduction: egg-laying followed by secretion of milk onto skin and hair in a mammary patch, in the absence of nipples. Offspring are highly immature at hatching and depend on oligosaccharide-rich milk for many months. The primary saccharide in long-beaked echidna milk is an acidic trisaccharide Neu4,5Ac2(α2-3)Gal(ß1-4)Glc (4-O-acetyl 3'-sialyllactose), but acidic oligosaccharides have not been characterized in platypus milk. In this study, acidic oligosaccharides purified from the carbohydrate fraction of platypus milk were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. All identified structures, except Neu5Ac(α2-3)Gal(ß1-4)Glc (3'-sialyllactose) contained Neu4,5Ac2 (4-O-acetyl-sialic acid). These include the trisaccharide 4-O-acetyl 3'-sialyllactose, the pentasaccharide Neu4,5Ac2(α2-3)Gal(ß1-4)GlcNAc(ß1-3)Gal(ß1-4)Glc (4-O-acetyl-3'-sialyllacto-N-tetraose d) and the hexasaccharide Neu4,5Ac2(α2-3)Gal(ß1-4)[Fuc(α1-3)]GlcNAc(ß1-3)Gal(ß1-4)Glc (4-O-acetyl-3'-sialyllacto-N-fucopentaose III). At least seven different octa- to deca-oligosaccharides each contained a lacto-N-neohexaose core (LNnH) and one or two Neu4,5Ac2 and one to three fucose residues. We conclude that platypus milk contains a diverse (≥ 20) array of neutral and acidic oligosaccharides based primarily on lactose, lacto-N-neotetraose (LNnT) and LNnH structural cores and shares with echidna milk the unique feature that all identified acidic oligosaccharides (other than 3'-sialyllactose) contain the 4-O-acetyl-sialic acid moiety. We propose that 4-O-acetylation of sialic acid moieties protects acidic milk oligosaccharides secreted onto integumental surfaces from bacterial hydrolysis via steric interference with bacterial sialidases. This may be of evolutionary significance since taxa ancestral to monotremes and other mammals are thought to have secreted milk, or a milk-like fluid containing oligosaccharides, onto skin surfaces.

Formation and Dynamics of Antiferromagnetic Correlations in Tunable Optical Lattices.

We report on the observation of antiferromagnetic correlations of ultracold fermions in a variety of optical lattice geometries that are well described by the Hubbard model, including dimers, 1D chains, ladders, isolated and coupled honeycomb planes, as well as square and cubic lattices. The dependence of the strength of spin correlations on the specific geometry is experimentally studied by measuring the correlations along different lattice tunneling links, where a redistribution of correlations between the different lattice links is observed. By measuring the correlations in a crossover between distinct geometries, we demonstrate an effective reduction of the dimensionality for our atom numbers and temperatures. We also investigate the formation and redistribution time of spin correlations by dynamically changing the lattice geometry and studying the time evolution of the system. Time scales ranging from a sudden quench of the lattice geometry to an adiabatic evolution are probed.