Structural atlas of a human gut crassvirus.

CrAssphage and related viruses of the order Crassvirales (hereafter referred to as crassviruses) were originally discovered by cross-assembly of metagenomic sequences. They are the most abundant viruses in the human gut, are found in the majority of individual gut viromes, and account for up to 95% of the viral sequences in some individuals1-4. Crassviruses are likely to have major roles in shaping the composition and functionality of the human microbiome, but the structures and roles of most of the virally encoded proteins are unknown, with only generic predictions resulting from bioinformatic analyses4,5. Here we present a cryo-electron microscopy reconstruction of Bacteroides intestinalis virus ΦcrAss0016, providing the structural basis for the functional assignment of most of its virion proteins. The muzzle protein forms an assembly about 1 MDa in size at the end of the tail and exhibits a previously unknown fold that we designate the 'crass fold', that is likely to serve as a gatekeeper that controls the ejection of cargos. In addition to packing the approximately 103 kb of virus DNA, the ΦcrAss001 virion has extensive storage space for virally encoded cargo proteins in the capsid and, unusually, within the tail. One of the cargo proteins is present in both the capsid and the tail, suggesting a general mechanism for protein ejection, which involves partial unfolding of proteins during their extrusion through the tail. These findings provide a structural basis for understanding the mechanisms of assembly and infection of these highly abundant crassviruses.

Quantum Work Statistics at Strong Reservoir Coupling.

Determining the statistics of work done on a quantum system while strongly coupled to a reservoir is a formidable task, requiring the calculation of the full eigenspectrum of the combined system and reservoir. Here, we show that this issue can be circumvented by using a polaron transformation that maps the system into a new frame where weak-coupling theory can be applied. Crucially, this polaron approach reproduces the Jarzynski fluctuation theorem, thus ensuring consistency with the laws of stochastic thermodynamics. We apply our formalism to a system driven across the Landau-Zener transition, where we identify clear signatures in the work distribution arising from a non-negligible coupling to the environment. Our results provide a new method for studying the stochastic thermodynamics of driven quantum systems beyond Markovian, weak-coupling regimes.

The DNA polymerase of bacteriophage YerA41 replicates its T-modified DNA in a primer-independent manner.

Yersinia phage YerA41 is morphologically similar to jumbo bacteriophages. The isolated genomic material of YerA41 could not be digested by restriction enzymes, and used as a template by conventional DNA polymerases. Nucleoside analysis of the YerA41 genomic material, carried out to find out whether this was due to modified nucleotides, revealed the presence of a ca 1 kDa substitution of thymidine with apparent oligosaccharide character. We identified and purified the phage DNA polymerase (DNAP) that could replicate the YerA41 genomic DNA even without added primers. Cryo-electron microscopy (EM) was used to characterize structural details of the phage particle. The storage capacity of the 131 nm diameter head was calculated to accommodate a significantly longer genome than that of the 145 577 bp genomic DNA of YerA41 determined here. Indeed, cryo-EM revealed, in contrast to the 25 Å in other phages, spacings of 33-36 Å between shells of the genomic material inside YerA41 heads suggesting that the heavily substituted thymidine increases significantly the spacing of the DNA packaged inside the capsid. In conclusion, YerA41 appears to be an unconventional phage that packages thymidine-modified genomic DNA into its capsids along with its own DNAP that has the ability to replicate the genome.

Effects of double-dose algebra on college persistence and degree attainment.

In 2003, Chicago Public Schools introduced double-dose algebra, requiring two periods of math-one period of algebra and one of algebra support-for incoming ninth graders with eighth-grade math scores below the national median. Using a regression discontinuity design, earlier studies showed promising results from the program: For median-skill students, double-dose algebra improved algebra test scores, pass rates, high school graduation rates, and college enrollment. This study follows the same students 12 y later. Our findings show that, for median-skill students in the 2003 cohort, double-dose significantly increased semesters of college attended and college degree attainment. These results were not replicated for the 2004 cohort. Importantly, the impact of the policy on median-skill students depended largely on how classes were organized. In 2003, the impacts on college persistence and degree attainment were large in schools that strongly adhered to the cut-score-based course assignment, but without grouping median-skill students with lower-skill peers. Few schools implemented the policy in such a way in 2004.

C-type cytochrome-initiated reduction of bacterial lytic polysaccharide monooxygenases.

The release of glucose from lignocellulosic waste for subsequent fermentation into biofuels holds promise for securing humankind's future energy needs. The discovery of a set of copper-dependent enzymes known as lytic polysaccharide monooxygenases (LPMOs) has galvanised new research in this area. LPMOs act by oxidatively introducing chain breaks into cellulose and other polysaccharides, boosting the ability of cellulases to act on the substrate. Although several proteins have been implicated as electron sources in fungal LPMO biochemistry, no equivalent bacterial LPMO electron donors have been previously identified, although the proteins Cbp2D and E from Cellvibrio japonicus have been implicated as potential candidates. Here we analyse a small c-type cytochrome (CjX183) present in Cellvibrio japonicus Cbp2D, and show that it can initiate bacterial CuII/I LPMO reduction and also activate LPMO-catalyzed cellulose-degradation. In the absence of cellulose, CjX183-driven reduction of the LPMO results in less H2O2 production from O2, and correspondingly less oxidative damage to the enzyme than when ascorbate is used as the reducing agent. Significantly, using CjX183 as the activator maintained similar cellulase boosting levels relative to the use of an equivalent amount of ascorbate. Our results therefore add further evidence to the impact that the choice of electron source can have on LPMO action. Furthermore, the study of Cbp2D and other similar proteins may yet reveal new insight into the redox processes governing polysaccharide degradation in bacteria.

Influence of Iron Deficiency on Clinical and Haemodynamic Parameters in Pulmonary Arterial Hypertension Cohorts.

BACKGROUND: Iron deficiency (Fedef) has been shown to be common in patients with group 1 or pulmonary arterial hypertension (PAH). Several studies have shown a negative impact of Fedef on clinical and haemodynamic parameters of the disease, but data from individual studies have not been strong enough to lead to incorporation of the finding of Fedef into prognostic or therapeutic algorithms. The goal of this meta-analysis was to combine data from available studies to better define any associations between Fedef and established variables of prognostic importance in PAH. METHODS: A literature search identified nine studies with extractable data relevant to the study questions. The impact of Fedef upon the following parameters was evaluated: 6-minute walk distance (6MWD), WHO-functional class, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, echocardiography, and findings from right heart catheterisation (RHC). Pooled results were reported as mean difference or risk difference with 95% confidence intervals utilising a random effects modeling approach. RESULTS: Fedef in the PAH population was common (47% of cases) and was associated with cardiovascular dysfunction (lower tricuspid annular plane systolic excursion [TAPSE], elevated NT-proBNP, and lower mixed venous oxygen saturation) and with reduction in functional capacity (lower 6MWD and higher functional class). CONCLUSION: This meta-analysis strengthens the relationships between Fedef and several markers of poor outcome in PAH. Fedef in patients with PAH warrants further scrutiny and merits consideration as a cause of clinical deterioration. Even though causation and longitudinal relationships between Fedef and PAH could not be identified, effect of Fedef on factors that affect disease prognosis is noteworthy and worthy of more focussed studies.

Phonon-Induced Optical Dephasing in Single Organic Molecules.

We present a joint experiment-theory analysis of the temperature-dependent emission spectra, zero-phonon linewidth, and second-order correlation function of light emitted from a single organic molecule. We observe spectra with a zero-phonon line together with several additional sharp peaks, broad phonon sidebands, and a strongly temperature dependent homogeneous broadening. Our model includes both localized vibrational modes of the molecule and a thermal phonon bath, which we include nonperturbatively, and is able to capture all observed features. For resonant driving we measure Rabi oscillations that become increasingly damped with temperature, which our model naturally reproduces. Our results constitute an essential characterization of the photon coherence of molecules, paving the way to their use in future quantum information applications.

Photon Statistics of Filtered Resonance Fluorescence.

Spectral filtering of resonance fluorescence is widely employed to improve single photon purity and indistinguishability by removing unwanted backgrounds. For filter bandwidths approaching the emitter linewidth, complex behavior is predicted due to preferential transmission of components with differing photon statistics. We probe this regime using a Purcell-enhanced quantum dot in both weak and strong excitation limits, finding excellent agreement with an extended sensor theory model. By changing only the filter width, the photon statistics can be transformed between antibunched, bunched, or Poissonian. Our results verify that strong antibunching and a subnatural linewidth cannot simultaneously be observed, providing new insight into the nature of coherent scattering.

Identification of human remains using Rapid DNA analysis.

Rapid identification of human remains following mass casualty events is essential to bring closure to family members and friends of the victims. Unfortunately, disaster victim identification, missing persons identification, and forensic casework analysis are often complicated by sample degradation due to exposure to harsh environmental conditions. Following a mass disaster, forensic laboratories may be overwhelmed by the number of dissociated portions that require identification and reassociation or compromised by the event itself. The interval between the disaster and receipt of victim samples at a laboratory is critical in that sample quality deteriorates as the postmortem interval increases. When bodies decompose due to delay in collection, transport, and sample processing, DNA becomes progressively fragmented, adversely impacting identification. We have previously developed a fully automated, field-forward Rapid DNA identification system that produces STR profiles (also referred to as DNA IDs or DNA fingerprints) from buccal and crime scene samples. The system performs all sample processing and data interpretation in less than 2 h. Here, we present results on Rapid DNA identification performed on several tissue types (including buccal, muscle, liver, brain, tooth, and bone) from exposed human bodies placed above ground or stored in a morgue/cooler, two scenarios commonly encountered following mass disasters. We demonstrate that for exposed remains, buccal swabs are the sample of choice for up to 11 days exposure and bone and tooth samples generated excellent DNA IDs for the 1-year duration of the study. For refrigerated remains, all sample types generated excellent DNA IDs for the 3-month testing period.

Environmental Nonadditivity and Franck-Condon physics in Nonequilibrium Quantum Systems.

We show that for a quantum system coupled to both vibrational and electromagnetic environments, enforcing additivity of their combined influences results in nonequilibrium dynamics that does not respect the Franck-Condon principle. We overcome this shortcoming by employing a collective coordinate representation of the vibrational environment, which permits the derivation of a nonadditive master equation. When applied to a two-level emitter our treatment predicts decreasing photon emission rates with increasing vibrational coupling, consistent with Franck-Condon physics. In contrast, the additive approximation predicts the emission rate to be completely insensitive to vibrations. We find that nonadditivity also plays a key role in the stationary nonequilibrium model behavior, enabling two-level population inversion under incoherent electromagnetic excitation.

Generating Maximal Entanglement between Spectrally Distinct Solid-State Emitters.

We show how to create maximal entanglement between spectrally distinct solid-state emitters embedded in a waveguide interferometer. By revealing the rich underlying structure of multiphoton scattering in emitters, we show that a two-photon input state can generate deterministic maximal entanglement even for emitters with significantly different transition energies and linewidths. The optimal frequency of the input is determined by two competing processes: which-path erasure and interaction strength. We find that smaller spectral overlap can be overcome with higher photon numbers, and quasimonochromatic photons are optimal for entanglement generation. Our work provides a new methodology for solid-state entanglement generation, where the requirement for perfectly matched emitters can be relaxed in favor of optical state optimization.

Light Scattering from Solid-State Quantum Emitters: Beyond the Atomic Picture.

Coherent scattering of light by a single quantum emitter is a fundamental process at the heart of many proposed quantum technologies. Unlike atomic systems, solid-state emitters couple to their host lattice by phonons. Using a quantum dot in an optical nanocavity, we resolve these interactions in both time and frequency domains, going beyond the atomic picture to develop a comprehensive model of light scattering from solid-state emitters. We find that even in the presence of a low-Q cavity with high Purcell enhancement, phonon coupling leads to a sideband that is completely insensitive to excitation conditions and to a nonmonotonic relationship between laser detuning and coherent fraction, both of which are major deviations from atomlike behavior.

8-Hydroxyquinolines are bactericidal against Mycobacterium tuberculosis.

There is an urgent need for new treatments effective against Mycobacterium tuberculosis, the causative agent of tuberculosis. The 8-hydroxyquinoline series is a privileged scaffold with anticancer, antifungal, and antibacterial activities. We conducted a structure-activity relationship study of the series regarding its antitubercular activity using 26 analogs. The 8-hydroxyquinolines showed good activity against M. tuberculosis, with minimum inhibitory concentrations (MIC90) of <5 µM for some analogs. Small substitutions at C5 resulted in the most potent activity. Substitutions at C2 generally decreased potency, although a sub-family of 2-styryl-substituted analogs retained activity. Representative compounds demonstrated bactericidal activity against replicating M. tuberculosis with >4 log kill at 10× MIC over 14 days. The majority of the compounds demonstrated cytotoxicity (IC50 of <100 µM). Further development of this series as antitubercular agents should address the cytotoxicity liability. However, the 8-hydroxyquinoline series represents a useful tool for chemical genomics to identify novel targets in M. tuberculosis.

Anodic Cyclization Reactions and the Mechanistic Strategies That Enable Optimization.

Oxidation reactions are powerful tools for synthesis because they allow us to reverse the polarity of electron-rich functional groups, generate highly reactive intermediates, and increase the functionality of molecules. For this reason, oxidation reactions have been and continue to be the subject of intense study. Central to these efforts is the development of mechanism-based strategies that allow us to think about the reactive intermediates that are frequently central to the success of the reactions and the mechanistic pathways that those intermediates trigger. For example, consider oxidative cyclization reactions that are triggered by the removal of an electron from an electron-rich olefin and lead to cyclic products that are functionalized for further elaboration. For these reactions to be successful, the radical cation intermediate must first be generated using conditions that limit its polymerization and then channeled down a productive desired pathway. Following the cyclization, a second oxidation step is necessary for product formation, after which the resulting cation must be quenched in a controlled fashion to avoid undesired elimination reactions. Problems can arise at any one or all of these steps, a fact that frequently complicates reaction optimization and can discourage the development of new transformations. Fortunately, anodic electrochemistry offers an outstanding opportunity to systematically probe the mechanism of oxidative cyclization reactions. The use of electrochemical methods allows for the generation of radical cations under neutral conditions in an environment that helps prevent polymerization of the intermediate. Once the intermediates have been generated, a series of "telltale indicators" can be used to diagnose which step in an oxidative cyclization is problematic for less successful transformation. A set of potential solutions to address each type of problem encountered has been developed. For example, problems with the initial cyclization reaction leading to either polymerization of the radical cation, elimination of a proton from or solvent trapping of that intermediate, or solvent trapping of the radical cation can be identified in the proton NMR spectrum of the crude reaction material. Such an NMR spectrum shows retention of the trapping group. The problems can be addressed by tuning the radical cation, altering the trapping group, or channeling the reactive intermediate down a radical pathway. Specific examples each are shown in this Account. Problems with the second oxidation step can be identified by poor current efficiency or general decomposition in spite of cyclic voltammetry evidence for a rapid cyclization. Solutions involve improving the oxidation conditions for the radical after cyclization by either the addition of a properly placed electron-donating group in the substrate or an increase in the concentration of electrolyte in the reaction (a change that stabilizes the cation generated from the second oxidation step). Problems with the final cation typically lead to overoxidation. Solutions to this problem require an approach that either slows down elimination side reactions or changes the reaction conditions so that the cation can be quickly trapped in an irreversible fashion. Again, this Account highlights these strategies along with the specific experimental protocols utilized.

Probing Electron-Phonon Interaction through Two-Photon Interference in Resonantly Driven Semiconductor Quantum Dots.

We investigate the temperature dependence of photon coherence properties through two-photon interference (TPI) measurements from a single quantum dot (QD) under resonant excitation. We show that the loss of indistinguishability is related only to the electron-phonon coupling and is not affected by spectral diffusion. Through these measurements and a complementary microscopic theory, we identify two independent separate decoherence processes, both of which are associated with phonons. Below 10 K, we find that the relaxation of the vibrational lattice is the dominant contribution to the loss of TPI visibility. This process is non-Markovian in nature and corresponds to real phonon transitions resulting in a broad phonon sideband in the QD emission spectra. Above 10 K, virtual phonon transitions to higher lying excited states in the QD become the dominant dephasing mechanism, this leads to a broadening of the zero phonon line, and a corresponding rapid decay in the visibility. The microscopic theory we develop provides analytic expressions for the dephasing rates for both virtual phonon scattering and non-Markovian lattice relaxation.

Energy transfer in structured and unstructured environments: Master equations beyond the Born-Markov approximations.

We explore excitonic energy transfer dynamics in a molecular dimer system coupled to both structured and unstructured oscillator environments. By extending the reaction coordinate master equation technique developed by Iles-Smith et al. [Phys. Rev. A 90, 032114 (2014)], we go beyond the commonly used Born-Markov approximations to incorporate system-environment correlations and the resultant non-Markovian dynamical effects. We obtain energy transfer dynamics for both underdamped and overdamped oscillator environments that are in perfect agreement with the numerical hierarchical equations of motion over a wide range of parameters. Furthermore, we show that the Zusman equations, which may be obtained in a semiclassical limit of the reaction coordinate model, are often incapable of describing the correct dynamical behaviour. This demonstrates the necessity of properly accounting for quantum correlations generated between the system and its environment when the Born-Markov approximations no longer hold. Finally, we apply the reaction coordinate formalism to the case of a structured environment comprising of both underdamped (i.e., sharply peaked) and overdamped (broad) components simultaneously. We find that though an enhancement of the dimer energy transfer rate can be obtained when compared to an unstructured environment, its magnitude is rather sensitive to both the dimer-peak resonance conditions and the relative strengths of the underdamped and overdamped contributions.

Solvolysis, Electrochemistry, and Development of Synthetic Building Blocks from Sawdust.

Either aldehyde or cinnamyl ether products can be selectively extracted from raw sawdust by controlling the temperature and pressure of a solvolysis reaction. These materials have been used as platform chemicals for the synthesis of 15 different synthetic substrates. The conversion of the initial sawdust-derived materials into electron-rich aryl substrates often requires the use of oxidation and reduction chemistry, and the role electrochemistry can play as a sustainable method for these transformations has been defined.

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions.

The combination of visible light, photovoltaics, and electrochemistry provides a convenient, inexpensive platform for conducting a wide variety of sustainable oxidation reactions. The approach presented in this article is compatible with both direct and indirect oxidation reactions, avoids the need for a stoichiometric oxidant, and leads to hydrogen gas as the only byproduct from the corresponding reduction reaction.

Suicidal Ideation in the Setting of Neurocysticercosis.

Neurocysticercosis (NCC) is considered a significant health concern in developing countries in parts of Asia, Africa, and Central and South America. However, with the increased immigration, it is now becoming increasingly prevalent in the United States. NCC has psychiatric implications often neglected and not recognized in the initial diagnostic workup of patients from developing countries suffering from seizures and psychiatric illnesses, such as depression. This case report aims to signify the presentation of NCC and illustrate the importance of the psychiatric manifestations of NCC in patients. We discuss the case of a 32-year-old female patient from a rural town in Central America who immigrated to New York and presented with uncontrolled seizures and symptomatic depression with suicidal ideations.

Structural dissection of two redox proteins from the shipworm symbiont Teredinibacter turnerae.

The discovery of lytic polysaccharide monooxygenases (LPMOs), a family of copper-dependent enzymes that play a major role in polysaccharide degradation, has revealed the importance of oxidoreductases in the biological utilization of biomass. In fungi, a range of redox proteins have been implicated as working in harness with LPMOs to bring about polysaccharide oxidation. In bacteria, less is known about the interplay between redox proteins and LPMOs, or how the interaction between the two contributes to polysaccharide degradation. We therefore set out to characterize two previously unstudied proteins from the shipworm symbiont Teredinibacter turnerae that were initially identified by the presence of carbohydrate binding domains appended to uncharacterized domains with probable redox functions. Here, X-ray crystal structures of several domains from these proteins are presented together with initial efforts to characterize their functions. The analysis suggests that the target proteins are unlikely to function as LPMO electron donors, raising new questions as to the potential redox functions that these large extracellular multi-haem-containing c-type cytochromes may perform in these bacteria.