Microscopic Evidence of Malaria Infection in Visceral Tissue from Medici Family, Italy.

Microscopy of mummified visceral tissue from a Medici family member in Italy identified a potential blood vessel containing erythrocytes. Giemsa staining, atomic force microscopy, and immunohistochemistry confirmed Plasmodium falciparum inside those erythrocytes. Our results indicate an ancient Mediterranean presence of P. falciparum, which remains responsible for most malaria deaths in Africa.

Spatial and temporal diversity of glycome expression in mammalian brain.

Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.

Second sound and the superfluid fraction in a Fermi gas with resonant interactions.

Superfluidity is a macroscopic quantum phenomenon occurring in systems as diverse as liquid helium and neutron stars. It occurs below a critical temperature and leads to peculiar behaviour such as frictionless flow, the formation of quantized vortices and quenching of the moment of inertia. Ultracold atomic gases offer control of interactions and external confinement, providing unique opportunities to explore superfluid phenomena. Many such (finite-temperature) phenomena can be explained in terms of a two-fluid mixture comprising a normal component, which behaves like an ordinary fluid, and a superfluid component with zero viscosity and zero entropy. The two-component nature of a superfluid is manifest in 'second sound', an entropy wave in which the superfluid and the non-superfluid components oscillate with opposite phases (as opposed to ordinary 'first sound', where they oscillate in phase). Here we report the observation of second sound in an ultracold Fermi gas with resonant interactions. The speed of second sound depends explicitly on the value of the superfluid fraction, a quantity that is sensitive to the spectrum of elementary excitations. Our measurements allow us to extract the temperature dependence of the superfluid fraction, a previously inaccessible quantity that will provide a benchmark for theories of strongly interacting quantum gases.

Probing the Interface of a Phase-Separated State in a Repulsive Bose-Fermi Mixture.

We probe the interface between a phase-separated Bose-Fermi mixture consisting of a small Bose-Einstein condensate of ^{41}K residing in a large Fermi sea of ^{6}Li. We quantify the residual spatial overlap between the two components by measuring three-body recombination losses for variable strength of the interspecies repulsion. A comparison with a numerical mean-field model highlights the importance of the kinetic energy term for the condensed bosons in maintaining the thin interface far into the phase-separated regime. Our results demonstrate a corresponding smoothing of the phase transition in a system of finite size.

Quantum Engineering of a Low-Entropy Gas of Heteronuclear Bosonic Molecules in an Optical Lattice.

We demonstrate a generally applicable technique for mixing two-species quantum degenerate bosonic samples in the presence of an optical lattice, and we employ it to produce low-entropy samples of ultracold ^{87}Rb^{133}Cs Feshbach molecules with a lattice filling fraction exceeding 30%. Starting from two spatially separated Bose-Einstein condensates of Rb and Cs atoms, Rb-Cs atom pairs are efficiently produced by using the superfluid-to-Mott insulator quantum phase transition twice, first for the Cs sample, then for the Rb sample, after nulling the Rb-Cs interaction at a Feshbach resonance's zero crossing. We form molecules out of atom pairs and characterize the mixing process in terms of sample overlap and mixing speed. The dense and ultracold sample of more than 5000 RbCs molecules is an ideal starting point for experiments in the context of quantum many-body physics with long-range dipolar interactions.

Decoherence of Impurities in a Fermi Sea of Ultracold Atoms.

We investigate the decoherence of ^{40}K impurities interacting with a three-dimensional Fermi sea of ^{6}Li across an interspecies Feshbach resonance. The decoherence is measured as a function of the interaction strength and temperature using a spin-echo atom interferometry method. For weak to moderate interaction strengths, we interpret our measurements in terms of scattering of K quasiparticles by the Fermi sea and find very good agreement with a Fermi liquid calculation. For strong interactions, we observe significant enhancement of the decoherence rate, which is largely independent of temperature, pointing to behavior that is beyond the scattering of quasiparticles in the Fermi liquid picture.

Lipidomic "deep profiling": an enhanced workflow to reveal new molecular species of signaling lipids.

Current mass spectrometry-based lipidomics aims to comprehensively cover wide ranges of lipid classes. We introduce a strategy to capture phospho-monoester lipids and improve the detection of long-chain base phosphates (LCB-Ps, e.g., sphingosine-1-phosphate). Ten novel LCB-Ps (d18:2, t20:1, odd carbon forms) were discovered and characterized in tissues from human and mouse, as well in D. melanogaster and S. cerevisiae. These findings have immediate relevance for our understanding of sphingosine-1-phosphate biosynthesis, signaling, and degradation.

Observation of the second triatomic resonance in Efimov's scenario.

We report the observation of a three-body recombination resonance in an ultracold gas of cesium atoms at a very large negative value of the s-wave scattering length. The resonance is identified as the second triatomic Efimov resonance, which corresponds to the situation where the first excited Efimov state appears at the threshold of three free atoms. This observation, together with a finite-temperature analysis and the known first resonance, allows the most accurate demonstration to date of the discrete scaling behavior at the heart of Efimov physics. For the system of three identical bosons, we obtain a scaling factor of 21.0(1.3), close to the ideal value of 22.7.

Observation of a strong atom-dimer attraction in a mass-imbalanced Fermi-Fermi mixture.

We investigate a mixture of ultracold fermionic K40 atoms and weakly bound Li6K40 dimers on the repulsive side of a heteronuclear atomic Feshbach resonance. By radio-frequency spectroscopy we demonstrate that the normally repulsive atom-dimer interaction is turned into a strong attraction. The phenomenon can be understood as a three-body effect in which two heavy K40 fermions exchange the light Li6 atom, leading to attraction in odd partial-wave channels (mainly p wave). Our observations show that mass imbalance in a fermionic system can profoundly change the character of interactions as compared to the well-established mass-balanced case.

Ultracold dense samples of dipolar RbCs molecules in the rovibrational and hyperfine ground state.

We produce ultracold dense trapped samples of ^{87}Rb^{133}Cs molecules in their rovibrational ground state, with full nuclear hyperfine state control, by stimulated Raman adiabatic passage (STIRAP) with efficiencies of 90%. We observe the onset of hyperfine-changing collisions when the magnetic field is ramped so that the molecules are no longer in the hyperfine ground state. A strong quadratic shift of the transition frequencies as a function of applied electric field shows the strongly dipolar character of the RbCs ground-state molecule. Our results open up the prospect of realizing stable bosonic dipolar quantum gases with ultracold molecules.

Laser cooling to quantum degeneracy.

We report on Bose-Einstein condensation in a gas of strontium atoms, using laser cooling as the only cooling mechanism. The condensate is formed within a sample that is continuously Doppler cooled to below 1 µK on a narrow-linewidth transition. The critical phase-space density for condensation is reached in a central region of the sample, in which atoms are rendered transparent for laser cooling photons. The density in this region is enhanced by an additional dipole trap potential. Thermal equilibrium between the gas in this central region and the surrounding laser cooled part of the cloud is established by elastic collisions. Condensates of up to 10(5) atoms can be repeatedly formed on a time scale of 100 ms, with prospects for the generation of a continuous atom laser.

Collective modes in a unitary Fermi gas across the superfluid phase transition.

We provide a joint theoretical and experimental investigation of the temperature dependence of the collective oscillations of first sound nature exhibited by a highly elongated harmonically trapped Fermi gas at unitarity, including the region below the critical temperature for superfluidity. Differently from the lowest axial breathing mode, the hydrodynamic frequencies of the higher-nodal excitations show a temperature dependence, which is calculated starting from Landau two-fluid theory and using the available experimental knowledge of the equation of state. The experimental results agree with high accuracy with the predictions of theory and provide the first evidence for the temperature dependence of the collective frequencies near the superfluid phase transition.

Recommendations for mass spectrometry data quality metrics for open access data (corollary to the Amsterdam Principles).

Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the United States National Cancer Institute convened the "International Workshop on Proteomic Data Quality Metrics" in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed up on two primary needs for the wide use of quality metrics: 1) an evolving list of comprehensive quality metrics and 2) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data. By agreement, this article is published simultaneously in the Journal of Proteome Research, Molecular and Cellular Proteomics, Proteomics, and Proteomics Clinical Applications as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals.

Recommendations for mass spectrometry data quality metrics for open access data (corollary to the Amsterdam principles).

Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the U.S. National Cancer Institute (NCI) convened the "International Workshop on Proteomic Data Quality Metrics" in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed upon two primary needs for the wide use of quality metrics: (i) an evolving list of comprehensive quality metrics and (ii) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data. By agreement, this article is published simultaneously in Proteomics, Proteomics Clinical Applications, Journal of Proteome Research, and Molecular and Cellular Proteomics, as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals.

Recommendations for mass spectrometry data quality metrics for open access data (corollary to the Amsterdam Principles).

Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the U.S. National Cancer Institute (NCI) convened the "International Workshop on Proteomic Data Quality Metrics" in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed up on two primary needs for the wide use of quality metrics: (1) an evolving list of comprehensive quality metrics and (2) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data. By agreement, this article is published simultaneously in the Journal of Proteome Research, Molecular and Cellular Proteomics, Proteomics, and Proteomics Clinical Applications as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals.

Employment of tandem mass spectrometry for the accurate and specific identification of oligosaccharide structures.

A method is described for the rapid identification of oligosaccharides employing a library of tandem MS spectra. Identification is aided by software that compares the sample tandem MS to those in the library. The method incorporates quadrupole time-of-flight mass spectrometry along with an annotated oligosaccharide (OS) structure library and the MassHunter Personal Compound Database and Library (PCDL) software. With an automated spectra search, OS structures in different samples are readily identified. This method is shown to be useful in the study of milk oligosaccharides but can be readily applied to oligosaccharide pools in other biological tissues.

Multiple precursor ion scanning of gangliosides and sulfatides with a reversed-phase microfluidic chip and quadrupole time-of-flight mass spectrometry.

Precise profiling of polar lipids including gangliosides and sulfatides is a necessary step in understanding the diverse physiological role of these lipids. We have established an efficient method for the profiling of polar lipids using reversed-phase nano high-performance liquid chromatography microfluidic chip quadrupole time-of-flight mass spectrometry (nano-HPLC-chip Q-TOF/MS). A microfluidic chip design provides improved chromatographic performance, efficient separation, and stable nanospray while the advanced high-resolution mass spectrometer allowed for the identification of complex isobaric polar lipids such as NeuAc- and NeuGc-containing gangliosides. Lipid classes were identified based on the characteristic fragmentation product ions generated during data-dependent tandem mass spectrometry (MS/MS) experiments. Each class was monitored by a postprocessing precursor ion scan. Relatively simple quantitation and identification of intact ions was possible due to the reproducible retention times provided by the nano-HPLC chip. The method described in this paper was used to profile polar lipids from mouse brain, which was found to contain 17 gangliosides and 13 sulfatides. Types and linkages of the monosaccharides and their acetyl modifications were identified by low-energy collision-induced dissociation (CID) (40 V), and the type of sphingosine base was identified by higher energy CID (80 V). Accurate mass measurements and chromatography unveiled the degree of unsaturation and hydroxylation in the ceramide lipid tails.

Identification and accurate quantitation of biological oligosaccharide mixtures.

Structure-specific characterization and quantitation is often required for effective functional studies of oligosaccharides. Inside the gut, HMOs are preferentially bound and catabolized by the beneficial bacteria. HMO utility by these bacteria employs structure-specific catabolism based on a number of glycosidases. Determining the activity of these enzymes requires accurate quantitation of a large number of structures. In this study, we describe a method for the quantitation of human milk oligosaccharide (HMO) structures employing LC/MS and isotopically labeled internal standards. Data analysis was accomplished with a newly developed software tool, LC/MS Searcher, that employs a reference structure library to process LC/MS data yielding structural identification with accurate quantitation. The method was used to obtain a meta-enzyme analysis of bacteria, the simultaneous characterization of all glycosidases employed by bacteria for the catabolism of milk oligosaccharides. Analysis of consumed HMO structures confirmed the utility of a ß-1,3-galactosidase in Bifidobacterium longum subsp. infantis ATCC 15697 (B. infantis). In comparison, Bifidobacterium breve ATCC 15700 showed significantly less HMO catabolic activity compared to B. infantis.

Creation of ultracold Sr(2) molecules in the electronic ground state.

We report on the creation of ultracold (84)Sr(2) molecules in the electronic ground state. The molecules are formed from atom pairs on sites of an optical lattice using stimulated Raman adiabatic passage (STIRAP). We achieve a transfer efficiency of 30% and obtain 4×10(4) molecules with full control over the external and internal quantum state. STIRAP is performed near the narrow (1)S(0)-(3)P(1) intercombination transition, using a vibrational level of the 1(0(u)(+)) potential as an intermediate state. In preparation of our molecule association scheme, we have determined the binding energies of the last vibrational levels of the 1(0(u)(+)), 1(1(u)) excited-state and the X (1)Σ(g)(+) ground-state potentials. Our work overcomes the previous limitation of STIRAP schemes to systems with magnetic Feshbach resonances, thereby establishing a route that is applicable to many systems beyond alkali-metal dimers.

Annotation and structural analysis of sialylated human milk oligosaccharides.

Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. Due to their negative charge and hydrophilic nature, they also help modulate cell-cell interactions. It has also been shown that sialic acids are involved in regulating the immune response and aid in brain development. In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. The precursor ions were further examined with collision-induced dissociation (CID). By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification.