Distinct roles of the Chlamydia trachomatis effectors TarP and TmeA in the regulation of formin and Arp2/3 during entry.

The obligate intracellular pathogen Chlamydia trachomatis manipulates the host actin cytoskeleton to assemble actin-rich structures that drive pathogen entry. The recent discovery of TmeA, which, like TarP, is an invasion-associated type III effector implicated in actin remodeling, raised questions regarding the nature of their functional interaction. Quantitative live-cell imaging of actin remodeling at invasion sites revealed differences in recruitment and turnover kinetics associated with the TarP and TmeA pathways, with the former accounting for most of the robust actin dynamics at invasion sites. TarP-mediated recruitment of actin nucleators, i.e. formins and the Arp2/3 complex, was crucial for rapid actin kinetics, generating a collaborative positive feedback loop that enhanced their respective actin-nucleating activities within invasion sites. In contrast, the formin Fmn1 was not recruited to invasion sites and did not collaborate with Arp2/3 within the context of TmeA-associated actin recruitment. Although the TarP-Fmn1-Arp2/3 signaling axis is responsible for the majority of actin dynamics, its inhibition had similar effects as the deletion of TmeA on invasion efficiency, consistent with the proposed model that TarP and TmeA act on different stages of the same invasion pathway.

Exploiting Nonclassical Motion of a Trapped Ion Crystal for Quantum-Enhanced Metrology of Global and Differential Spin Rotations.

We theoretically investigate prospects for the creation of nonclassical spin states in trapped ion arrays by coupling to a squeezed state of the collective motion of the ions. The correlations of the generated spin states can be tailored for quantum-enhanced sensing of global or differential rotations of subensembles of the spins by working with specific vibrational modes of the ion array. We propose a pair of protocols to utilize the generated states and demonstrate their viability even for small systems, while assessing limitations imposed by spin-motion entanglement and technical noise. Our work suggests new opportunities for the preparation of many-body states with tailored correlations for quantum-enhanced metrology in spin-boson systems.

Emergence of multi-body interactions in a fermionic lattice clock.

Alkaline-earth atoms have metastable 'clock' states with minute-long optical lifetimes, high-spin nuclei and SU(N)-symmetric interactions, making them powerful platforms for atomic clocks1, quantum information processing2 and quantum simulation3. Few-particle systems of such atoms provide opportunities to observe the emergence of complex many-body phenomena with increasing system size4. Multi-body interactions among particles are emergent phenomena, which cannot be broken down into sums over underlying pairwise interactions. They could potentially be used to create exotic states of quantum matter5,6, but have yet to be explored in ultracold fermions. Here we create arrays of isolated few-body systems in an optical clock based on a three-dimensional lattice of fermionic 87Sr atoms. We use high-resolution clock spectroscopy to directly observe the onset of elastic and inelastic multi-body interactions among atoms. We measure the frequency shifts of the clock transition for varying numbers of atoms per lattice site, from n = 1 to n = 5, and observe nonlinear interaction shifts characteristic of elastic multi-body effects. These measurements, combined with theory, elucidate an emergence of SU(N)-symmetric multi-body interactions, which are unique to fermionic alkaline-earth atoms. To study inelastic multi-body effects, we use these frequency shifts to isolate n-occupied sites in the lattice and measure the corresponding lifetimes of the clock states. This allows us to access the short-range few-body physics without experiencing the systematic effects that are encountered in a bulk gas. The lifetimes that we measure in the isolated few-body systems agree very well with numerical predictions based on a simple model for the interatomic potential, suggesting a universality in ultracold collisions. By connecting these few-body systems through tunnelling, the favourable energy and timescales of the interactions will allow our system to be used for studies of high-spin quantum magnetism7,8 and the Kondo effect3,9.

Spin-orbit-coupled fermions in an optical lattice clock.

Engineered spin-orbit coupling (SOC) in cold-atom systems can enable the study of new synthetic materials and complex condensed matter phenomena. However, spontaneous emission in alkali-atom spin-orbit-coupled systems is hindered by heating, limiting the observation of many-body effects and motivating research into potential alternatives. Here we demonstrate that spin-orbit-coupled fermions can be engineered to occur naturally in a one-dimensional optical lattice clock. In contrast to previous SOC experiments, here the SOC is both generated and probed using a direct ultra-narrow optical clock transition between two electronic orbital states in 87Sr atoms. We use clock spectroscopy to prepare lattice band populations, internal electronic states and quasi-momenta, and to produce spin-orbit-coupled dynamics. The exceptionally long lifetime of the excited clock state (160 seconds) eliminates decoherence and atom loss from spontaneous emission at all relevant experimental timescales, allowing subsequent momentum- and spin-resolved in situ probing of the SOC band structure and eigenstates. We use these capabilities to study Bloch oscillations, spin-momentum locking and Van Hove singularities in the transition density of states. Our results lay the groundwork for using fermionic optical lattice clocks to probe new phases of matter.

Men who have sex with men experience low anxiety and few barriers to performing anal self or companion examinations: a qualitative study of the Prevent Anal Cancer Palpation Study.

While rare in the larger population, anal cancer incidence is significantly higher in groups such as sexual minority men and people living with HIV. This qualitative analysis examined participants' experiences and perceptions of barriers to anal self-examination and anal companion examination through interviews completed as a part of a larger clinical trial. Interviews were conducted online with participants (n = 131) within a week of their baseline appointment between January 2020 and October 2021. Content analysis denoted participants' thoughts and perceptions about anal self-examination and anal companion examinations. Of the 131 cisgender men interviewed (mean age 49.9 years, SD 12.7), 92.4% identified as gay, 54.9% identified as white, 22.1% identified as Black, 19.9% identified as Latino, and 44.3% of participants were living with HIV. Participants did not report feelings of excessive anxiety when an abnormality was detected. However, three salient themes emerged as to why participants may not perform an anal self-examination or anal companion examination: (1) physical limitation(s), (2) potential sexualisation of the examination, and (3) level of comfort discussing anal health. Future work must continue to explore methods that not only decrease stigma surrounding anal health but also bolster feelings of accessibility to perform self and couple examinations.

The asymptotic distribution of the permutation entropy.

Ordinal patterns serve as a robust symbolic transformation technique, enabling the unveiling of latent dynamics within time series data. This methodology involves constructing histograms of patterns, followed by the calculation of both entropy and statistical complexity-an avenue yet to be fully understood in terms of its statistical properties. While asymptotic results can be derived by assuming a multinomial distribution for histogram proportions, the challenge emerges from the non-independence present in the sequence of ordinal patterns. Consequently, the direct application of the multinomial assumption is questionable. This study focuses on the computation of the asymptotic distribution of permutation entropy, considering the inherent patterns' correlation structure. Furthermore, the research delves into a comparative analysis, pitting this distribution against the entropy derived from a multinomial law. We present simulation algorithms for sampling time series with prescribed histograms of patterns and transition probabilities between them. Through this analysis, we better understand the intricacies of ordinal patterns and their statistical attributes.

Detection of cardiac arrhythmia patterns in ECG through H × C plane.

The aim of this study is to formulate a new methodology based upon informational tools to detect patients with cardiac arrhythmias. As it is known, sudden death is the consequence of a final arrhythmia, and here lies the relevance of the efforts aimed at the early detection of arrhythmias. The information content in the time series from an electrocardiogram (ECG) signal is conveyed in the form of a probability distribution function, to compute the permutation entropy proposed by Bandt and Pompe. This selection was made seeking its remarkable conceptual simplicity, computational speed, and robustness to noise. In this work, two well-known databases were used, one containing normal sinus rhythms and another one containing arrhythmias, both from the MIT medical databank. For different values of embedding time delay τ, normalized permutation entropy and statistical complexity measure are computed to finally represent them on the horizontal and vertical axes, respectively, which define the causal plane H×C. To improve the results obtained in previous works, a feature set composed by these two magnitudes is built to train the following supervised machine learning algorithms: random forest (RF), support vector machine (SVM), and k nearest neighbors (kNN). To evaluate the performance of each classification technique, a 10-fold cross-validation scheme repeated 10 times was implemented. Finally, to select the best model, three quality parameters were computed, namely, accuracy, the area under the receiver operative characteristic (ROC) curve (AUC), and the F1-score. The results obtained show that the best classification model to detect the ECG coming from arrhythmic patients is RF. The values of the quality parameters were at the same levels reported in the available literature using a larger data set, thus supporting this proposal that uses a very small-sized feature space to train the model later used to classify. Summarizing, the attained results show the possibility to discriminate both groups of patients, with normal sinus rhythm or arrhythmic ECG, showing a promising efficiency in the definition of new markers for the detection of cardiovascular pathologies.

Statistical properties of the entropy from ordinal patterns.

The ultimate purpose of the statistical analysis of ordinal patterns is to characterize the distribution of the features they induce. In particular, knowing the joint distribution of the pair entropy-statistical complexity for a large class of time series models would allow statistical tests that are unavailable to date. Working in this direction, we characterize the asymptotic distribution of the empirical Shannon's entropy for any model under which the true normalized entropy is neither zero nor one. We obtain the asymptotic distribution from the central limit theorem (assuming large time series), the multivariate delta method, and a third-order correction of its mean value. We discuss the applicability of other results (exact, first-, and second-order corrections) regarding their accuracy and numerical stability. Within a general framework for building test statistics about Shannon's entropy, we present a bilateral test that verifies if there is enough evidence to reject the hypothesis that two signals produce ordinal patterns with the same Shannon's entropy. We applied this bilateral test to the daily maximum temperature time series from three cities (Dublin, Edinburgh, and Miami) and obtained sensible results.

An analysis of contact tracing protocol in an over-dispersed SEIQR Covid-like disease.

The aim of this work is to study an over-dispersed SEIQR infectious disease and obtain optimal methods of contact tracing. A prototypical example of such a disease is that of the current SARS-CoV-2 pandemic. In consequence, this study is immediately applicable to the current health crisis. In this paper, we introduce both a discrete and continuous model for various modes of contact tracing. From the continuous model, we derive a basic reproductive number and study the stability of the equilibrium points. We also implement the continuous and discrete models numerically and further analyze the effectiveness of different types of contact tracing and their cost on society. Additionally, through these simulations, we also study the effect that various parameters of the disease have on its evolution.

Suicidality among bisexual youths: the role of parental sexual orientation support and concealment.

Compared with the heterosexual population, the prevalence of mental health outcomes such as suicidality (suicidal ideation, suicide plans, and suicide attempts) is higher among sexual minority youth, particularly those who identify themselves as bisexuals. Bisexuals are at an even elevated risk within the LGB populations due to biphobia, monosexism, bisexual invisibility or erasure, and lack of support resources. These experiences may bring about issues regarding concealment of their sexual orientation linked to suicidality. Studies have also identified that parental support is a protective factor against suicidality among the youth, particularly their sexual orientation. The present study used a cross-sectional, predictive research design to examine parental sexual orientation support and concealment and their associations and predictive abilities in the suicidality of 151 Filipino bisexual youths aged 18-24 years old. The participants were recruited online within six months, from July 2021 to December 2021. As measured by the Parental Support for Sexual Orientation Scale, Sexual Orientation Concealment Scale, and Suicide Behaviors Questionnaire-Revised, results showed that among our bisexual participants, parental sexual orientation support and concealment did not have a significant relationship with and could not predict their risk for suicidality. Limitations and suggestions for further research were discussed, considering our findings.

A post-invasion role for Chlamydia type III effector TarP in modulating the dynamics and organization of host cell focal adhesions.

The human pathogen Chlamydia trachomatis targets epithelial cells lining the genital mucosa. We observed that infection of various cell types, including fibroblasts and epithelial cells resulted in the formation of unusually stable and mature focal adhesions that resisted disassembly induced by the myosin II inhibitor, blebbistatin. Superresolution microscopy revealed in infected cells the vertical displacement of paxillin and focal adhesion kinase from the signaling layer of focal adhesions, whereas vinculin remained in its normal position within the force transduction layer. The candidate type III effector TarP, which localized to focal adhesions during infection and when expressed ectopically, was sufficient to mimic both the reorganization and blebbistatin-resistant phenotypes. These effects of TarP, including its localization to focal adhesions, required a post-invasion interaction with the host protein vinculin through a specific domain at the C terminus of TarP. This interaction is repurposed from an actin-recruiting and -remodeling complex to one that mediates nanoarchitectural and dynamic changes of focal adhesions. The consequence of Chlamydia-stabilized focal adhesions was restricted cell motility and enhanced attachment to the extracellular matrix. Thus, via a novel mechanism, Chlamydia inserts TarP within focal adhesions to alter their organization and stability.

Dipole-Dipole Frequency Shifts in Multilevel Atoms.

Dipole-dipole interactions lead to frequency shifts that are expected to limit the performance of next-generation atomic clocks. In this work, we compute dipolar frequency shifts accounting for the intrinsic atomic multilevel structure in standard Ramsey spectroscopy. When interrogating the transitions featuring the smallest Clebsch-Gordan coefficients, we find that a simplified two-level treatment becomes inappropriate, even in the presence of large Zeeman shifts. For these cases, we show a net suppression of dipolar frequency shifts and the emergence of dominant nonclassical effects for experimentally relevant parameters. Our findings are pertinent to current generations of optical lattice and optical tweezer clocks, opening a way to further increase their current accuracy, and thus their potential to probe fundamental and many-body physics.

Entangling two transportable neutral atoms via local spin exchange.

To advance quantum information science, physical systems are sought that meet the stringent requirements for creating and preserving quantum entanglement. In atomic physics, robust two-qubit entanglement is typically achieved by strong, long-range interactions in the form of either Coulomb interactions between ions or dipolar interactions between Rydberg atoms. Although such interactions allow fast quantum gates, the interacting atoms must overcome the associated coupling to the environment and cross-talk among qubits. Local interactions, such as those requiring substantial wavefunction overlap, can alleviate these detrimental effects; however, such interactions present a new challenge: to distribute entanglement, qubits must be transported, merged for interaction, and then isolated for storage and subsequent operations. Here we show how, using a mobile optical tweezer, it is possible to prepare and locally entangle two ultracold neutral atoms, and then separate them while preserving their entanglement. Ground-state neutral atom experiments have measured dynamics consistent with spin entanglement, and have detected entanglement with macroscopic observables; we are now able to demonstrate position-resolved two-particle coherence via application of a local gradient and parity measurements. This new entanglement-verification protocol could be applied to arbitrary spin-entangled states of spatially separated atoms. The local entangling operation is achieved via spin-exchange interactions, and quantum tunnelling is used to combine and separate atoms. These techniques provide a framework for dynamically entangling remote qubits via local operations within a large-scale quantum register.

Detecting Out-of-Time-Order Correlations via Quasiadiabatic Echoes as a Tool to Reveal Quantum Coherence in Equilibrium Quantum Phase Transitions.

We propose a new dynamical method to connect equilibrium quantum phase transitions and quantum coherence using out-of-time-order correlations (OTOCs). Adopting the iconic Lipkin-Meshkov-Glick and transverse-field Ising models as illustrative examples, we show that an abrupt change in coherence and entanglement of the ground state across a quantum phase transition is observable in the spectrum of multiple quantum coherence intensities, which are a special type of OTOC. We also develop a robust protocol to obtain the relevant OTOCs using quasi-adiabatic quenches through the ground state phase diagram. Our scheme allows for the detection of OTOCs without time reversal of coherent dynamics, making it applicable and important for a broad range of current experiments where time reversal cannot be achieved by inverting the sign of the underlying Hamiltonian.

Manipulation of the Host Cell Cytoskeleton by Chlamydia.

Chlamydiae are obligate intracellular pathogens. They undergo a biphasic developmental cycle differentiating between the infectious but metabolically quiescent elementary body and the vegetative, but non-infectious reticulate body. Chlamydia spends a significant portion of its development in the non-infectious stage, demanding an effective strategy of manipulating the host cells to ensure its intracellular survival and replication. A common target of all Chlamydia species studied so far is the host cell cytoskeleton, with past and recent findings revealing crucial roles in invasion, inclusion maintenance, nutrient acquisition, and egress. The molecular details of how Chlamydia co-opts the cytoskeleton is becoming clearer, with bacterial factors and their corresponding host cell targets identified.

Dark States of Multilevel Fermionic Atoms in Doubly Filled Optical Lattices.

We propose to use fermionic atoms with degenerate ground and excited internal levels (F_{g}→F_{e}), loaded into the motional ground state of an optical lattice with two atoms per lattice site, to realize dark states with no radiative decay. The physical mechanism behind the dark states is an interplay of Pauli blocking and multilevel dipolar interactions. The dark states are independent of lattice geometry, can support an extensive number of excitations, and can be coherently prepared using a Raman scheme taking advantage of the quantum Zeno effect. These attributes make them appealing for atomic clocks, quantum memories, and quantum information on decoherence free subspaces.

Cluster State Generation with Spin-Orbit Coupled Fermionic Atoms in Optical Lattices.

Measurement-based quantum computation, an alternative paradigm for quantum information processing, uses simple measurements on qubits prepared in cluster states, a class of multiparty entangled states with useful properties. Here we propose and analyze a scheme that takes advantage of the interplay between spin-orbit coupling and superexchange interactions, in the presence of a coherent drive, to deterministically generate macroscopic arrays of cluster states in fermionic alkaline earth atoms trapped in three dimensional (3D) optical lattices. The scheme dynamically generates cluster states without the need of engineered transport, and is robust in the presence of holes, a typical imperfection in cold atom Mott insulators. The protocol is of particular relevance for the new generation of 3D optical lattice clocks with coherence times >10 s, 2 orders of magnitude larger than the cluster state generation time. We propose the use of collective measurements and time reversal of the Hamiltonian to benchmark the underlying Ising model dynamics and the generated many-body correlations.

Pathogenic Puppetry: Manipulation of the Host Actin Cytoskeleton by Chlamydia trachomatis.

The actin cytoskeleton is crucially important to maintenance of the cellular structure, cell motility, and endocytosis. Accordingly, bacterial pathogens often co-opt the actin-restructuring machinery of host cells to access or create a favorable environment for their own replication. The obligate intracellular organism Chlamydia trachomatis and related species exemplify this dynamic: by inducing actin polymerization at the site of pathogen-host attachment, Chlamydiae induce their own uptake by the typically non-phagocytic epithelium they infect. The interaction of chlamydial adhesins with host surface receptors has been implicated in this effect, as has the activity of the chlamydial effector TarP (translocated actin recruitment protein). Following invasion, C. trachomatis dynamically assembles and maintains an actin-rich cage around the pathogen's membrane-bound replicative niche, known as the chlamydial inclusion. Through further induction of actin polymerization and modulation of the actin-crosslinking protein myosin II, C. trachomatis promotes egress from the host via extrusion of the inclusion. In this review, we present the experimental findings that can inform our understanding of actin-dependent chlamydial pathogenesis, discuss lingering questions, and identify potential avenues of future study.

Fat accumulation, fatty acids and melting point changes in broiler chick abdominal fat as affected by time of dietary fat feeding and slaughter age.

1. This work aims to quantify changes in fatty acid profile, melting point, abdominal fat accumulation and 2-thiobarbituric acid-reactive substances production depending on dietary fat source and age at slaughter, and to estimate the optimal date for the change from an unsaturated fat to a saturated fat diet or vice versa. 2. Treatments established were (1) birds fed 8% tallow from 21 to 49 d (TTT); (2) birds fed 8% tallow from 21 to 37 d and 8% sunflower oil from d 38 to 49 (TSS); (3) birds fed 8% sunflower oil from 21 to 37 d and 8% tallow from d 38 to 49 (STT); (4) birds fed 8% sunflower oil from 21 to 41 d and 8% tallow from d 42 to 49 (SST); (5) birds fed 8% sunflower oil from 21 to 49 d (SSS). Birds from each group were slaughtered on d 21, 29, 38, 40, 42, 44, 46 and 49. 3. The polyunsaturated fatty acids (PUFAs) proportion in the SSS group reached maximum values at d 40 and fitted a quadratic response. This group also showed a decrease in saturated fatty acids (SATs) and monounsaturated fatty acids (MUFAs) of lower intensity than the PUFA increase. The highest synthesis of SAT + MUFA was found in the SSS and TSS groups, whereas these had the lowest body-to-dietary PUFA ratio. 4. A high and quadratic increase in the MUFA proportion was observed during the first 10 d of feeding with the tallow-enriched diet at the expenses of the proportion of PUFA that quadratically decreased (minimum values at d 38). 5. Lipogenic and desaturation capacity decreased with age. 6. The TSS group increased tissue PUFA content faster that the SST group decreased PUFA content after the change in diet which indicates that the earlier feeding has to be taken into consideration for obtaining higher or lower changes in quality parameters. 7. The melting point of the SSS group showed a lower response to the dietary treatment in the initial period when compared to the TTT treatment. 8. The TTT, STT, SST and TSS groups showed similar fat accumulation, and changes in lipid oxidation were related to the day of dietary sunflower oil supplementation. 9. Based on the results, it would be possible to determine the most appropriate dietary programme and optimum slaughter age to obtain chicken meat with the desired quality characteristics.

The influence of mitochondrial dynamics on mitochondrial genome stability.

Mitochondria are dynamic organelles that fuse and divide. These changes alter the number and distribution of mitochondrial structures throughout the cell in response to developmental and metabolic cues. We have demonstrated that mitochondrial fission is essential to the maintenance of mitochondrial DNA (mtDNA) under changing metabolic conditions in wild-type Saccharomyces cerevisiae. While increased loss of mtDNA integrity has been demonstrated for dnm1-∆ fission mutants after growth in a non-fermentable carbon source, we demonstrate that growth of yeast in different carbon sources affects the frequency of mtDNA loss, even when the carbon sources are fermentable. In addition, we demonstrate that the impact of fission on mtDNA maintenance during growth in different carbon sources is neither mediated by retrograde signaling nor mitophagy. Instead, we demonstrate that mitochondrial distribution and mtDNA maintenance phenotypes conferred by loss of Dnm1p are suppressed by the loss of Sod2p, the mitochondrial matrix superoxide dismutase.