Browse Articles

Maternal occupational exposures during early stages of pregnancy and adverse birth outcomes in the NINFEA birth-cohort

Objectives Maternal occupational exposures during early pregnancy can be detrimental to foetus health and have short- and long-term health effects on the child. This study examined their association with adverse birth outcomes. Methods The study included 3938 nulliparous women from the Italian NINFEA mother-child cohort. Their occupational exposures during the first trimester of pregnancy were assessed through prospectively collected questionnaire information and job-exposure matrices. Associations between maternal exposures and birthweight, preterm birth, and delivery by caesarean section were analysed by multivariable linear and logistic regression models. An exploratory factor analysis was carried out to explore co-exposure profiles in association with birth outcomes. Results Women exposed to passive smoking at work and those who reduced their working hours during pregnancy were found to have an increased likelihood of all analysed birth outcomes. Children of mothers performing a demanding work were less likely to be born preterm [OR 0.72 (95% CI 0.54 to 0.95)] and more likely to have a higher birthweight [β = 40.4 g (95% CI 7.5 to 73.4)]. Maternal exposures to heat and dust were associated with a lower birthweight [β = -160.1 g (95% CI -299.6 to -20.7)] and increased odds of caesarean section [OR 6.99 (95% CI 2.36 to 25.47)], respectively. Conclusions This study provides some evidence of the selection of healthy population into the workforce and of association between work-related passive smoking, heat and dust and adverse birth outcomes.

Accurate machine learning of rate coefficients for state-to-state transitions in molecular collisions

We present an algorithm that combines quantum scattering calculations with probabilistic machine-learning models to predict quantum dynamics rate coefficients for a large number of state-to-state transitions in molecule–molecule collisions much faster than with direct solutions of the Schrödinger equation. By utilizing the predictive power of Gaussian process regression with kernels, optimized to make accurate predictions outside of the input parameter space, the present strategy reduces the computational cost by about 75%, with an accuracy within 5%. Our method uses temperature dependences of rate coefficients for transitions from the isolated states of initial rotational angular momentum j, determined via explicit calculations, to predict the temperature dependences of rate coefficients for other values of j. The approach, demonstrated here for rovibrational transitions of SiO due to thermal collisions with H2, uses different prediction models and is thus adaptive to various time and accuracy requirements. The procedure outlined in this work can be used to extend multiple inelastic molecular collision databases without exponentially large computational resources required for conventional rigorous quantum dynamics calculations.

A computational study on the effect of structural isomerism on the excited state lifetime and redox energetics of archetype iridium photoredox catalyst platforms [Ir(ppy)2(bpy)]+ and Ir(ppy)3

This study investigates the impact of structural isomerism on the excited state lifetime and redox energetics of heteroleptic [Ir(ppy)2(bpy)]+ and homoleptic Ir(ppy)3 photoredox catalysts using ground-state and time-dependent density functional theory methods. While the ground- and excited-state reduction potentials differ only slightly among the isomers of these complexes, our findings reveal significant variations in the radiative and non-radiative decay rates of the reactivity-controlling triplet 3MLCT states of these closely related species. The observed differences in radiative decay rates could be traced back to variations in the transition dipole moment, vertical energy gaps, and spin–orbit coupling of the isomers. In [Ir(ppy)2(bpy)]+, transition dipole moment differences play a significant role in controlling the relative lifetime of the triplet states, which we rationalized by a vectorial analysis of permanent dipole moments of the ground and excited states. Regarding the two isomers of Ir(ppy)3, changes in radiative decay rates were primarily attributed to variations in vertical energy gaps and intensity borrowing from other singlet-singlet transitions driven by spin–orbit coupling. Non-radiative decay variations were assessed in terms of differences in reorganization energies, adiabatic energy gap, and spin–orbit coupling. For both complexes, reorganization energies associated with low-energy molecular vibrations and metal–ligand bond length changes following the de-excitation process were major contributors. These insights provide a deeper understanding of how molecular design can be leveraged to optimize the performance of iridium-based photoredox catalysts, potentially guiding the development of more efficient catalytic systems for future applications.

Electronic spectroscopy and excited state mixing of OThF

Electronic spectra for OThF have been recorded using fluorescence excitation and two-photon resonantly enhanced ionization techniques. Multiple vibronic bands were observed in the 340–460 nm range. Dispersed fluorescence spectra provided ground state vibrational constants and evidence of extensive vibronic state mixing at higher excitation energies. Two-photon ionization measurements established the ionization energy for OThF of 6.283(5) eV. To guide the assignment of the OThF spectra, electronic structure calculations were carried out using relativistic equation-of-motion coupled-cluster singles and doubles methods. These calculations indicated that spin–orbit induced mixing of the 32A″ and 42A′ states was mediated by a seam of potential energy surface intersections.

Modeling DNA methyltransferase function to predict epigenetic correlation patterns in healthy and cancer cells

DNA methylation is a crucial epigenetic modification that orchestrates chromatin remodelers that suppress transcription, and aberrations in DNA methylation result in a variety of conditions such as cancers and developmental disorders. While it is understood that methylation occurs at CpG-rich DNA regions, it is less understood how distinct methylation profiles are established within various cell types. In this work, we develop a molecular-transport model that depicts the genomic exploration of DNA methyltransferase within a multiscale DNA environment, incorporating biologically relevant factors like methylation rate and CpG density to predict how patterns are established. Our model predicts DNA methylation-state correlation distributions arising from the transport and kinetic properties that are crucial for the establishment of unique methylation profiles. We model the methylation correlation distributions of nine cancerous human cell types to determine how these properties affect the epigenetic profile. Our theory is capable of recapitulating experimental methylation patterns, suggesting the importance of DNA methyltransferase transport in epigenetic regulation. Through this work, we propose a mechanistic description for the establishment of methylation profiles, capturing the key behavioral characteristics of methyltransferase that lead to aberrant methylation.

Anion photoelectron velocity-map imaging using a tunable laser at a 100 kHz repetition rate

We present velocity-map imaging (VMI) of photoelectrons detached from anions using an optical parametric amplifier operating at a repetition rate as high as 100 kHz. The light source generates femtosecond (fs) laser pulses tunable from near-infrared to ultraviolet (310–2600 nm), which interact synchronously with mass-selected anion bunches. We demonstrate this technique by measuring two-dimensional projections of photoelectrons ejected from silver trimer anions, Ag3−, across a photon energy range from 2.43 to 4.00 eV (509–310 nm), with an average power of 50–300 mW. This high-repetition-rate VMI setup allows rapid data acquisition of photoelectron spectra and laboratory-frame photoelectron angular distributions of anions at various photon energies, facilitating investigation of their electronic and geometric structures. Taking advantage of the fs pulses, this approach will also enable time-resolved photoelectron imaging for tracking electronic and nuclear dynamics of anions with high efficiency.

Slower swimming promotes chemotactic encounters between bacteria and small phytoplankton

Chemotaxis enables marine bacteria to increase encounters with phytoplankton cells by reducing their search times, provided that bacteria detect noisy chemical gradients around phytoplankton. Gradient detection depends on bacterial phenotypes and phytoplankton size: large phytoplankton produce spatially extended but shallow gradients, whereas small phytoplankton produce steeper but spatially more confined gradients. To date, it has remained unclear how phytoplankton size and bacterial swimming speed affect bacteria’s gradient detection ability and search times for phytoplankton. Here, we compute an upper bound on the increase in bacterial encounter rate with phytoplankton due to chemotaxis over random motility alone. We find that chemotaxis can substantially decrease search times for small phytoplankton, but this advantage is highly sensitive to variations in bacterial phenotypes or phytoplankton leakage rates. By contrast, chemotaxis toward large phytoplankton cells reduces the search time more modestly, but this benefit is more robust to variations in search or environmental parameters. Applying our findings to marine phytoplankton communities, we find that, in productive waters, chemotaxis toward phytoplankton smaller than 2 μm provides little to no benefit, but can decrease average search times for large phytoplankton (∼20 μm) from 2 wk to 2 d, an advantage that is robust to variations and favors bacteria with higher swimming speeds. By contrast, in oligotrophic waters, chemotaxis can reduce search times for picophytoplankton (∼1 μm) up to 10-fold, from a week to half a day, but only for bacteria with low swimming speeds and long sensory timescales. This asymmetry may promote the coexistence of diverse search phenotypes in marine bacterial populations.

Pair approximating the action for molecular rotations in path integral Monte Carlo

Typical path integral Monte Carlo approaches use the primitive approximation to compute the probability density for a given path. In this work, we develop the pair discrete variable representation (pair-DVR) approach to study molecular rotations. The pair propagator, which was initially introduced to study superfluidity in condensed helium, is naturally well-suited for systems interacting with a pairwise potential. Consequently, paths sampled using the pair action tend to be closer to the exact paths (compared to primitive Trotter paths) for such systems leading to convergence with less imaginary time steps. Our approach relies on using the pair factorization approach in conjunction with a discretized path integral ground state paradigm to study a chain of planar rotors interacting with a pairwise dipole interaction. We first use the Wigner–Kirkwood density expansion to analyze the asymptotics of the pair propagator in imaginary time. Then, we exhibit the utility of the pair factorization scheme via convergence studies comparing the pair and primitive propagators. Finally, we compute energetic and structural properties of this system including the correlation function and Binder ratio as functions of the coupling strength to examine the behavior of the pair-DVR method near criticality. The density matrix renormalization group results are used for benchmarking throughout.

Strong adsorption of guanidinium cations to the air–water interface

Combining Deep-UV second harmonic generation spectroscopy with molecular simulations, we confirm and quantify the specific adsorption of guanidinium cations to the air–water interface. Using a Langmuir analysis of measurements at multiple concentrations, we extract the Gibbs free energy of adsorption, finding it larger than typical thermal energies. Molecular simulations clarify the role of polarizability in tuning the thermodynamics of adsorption, and establish the preferential parallel alignment of guanidinium at the air–water interface. As a polyatomic cation, guanidinium represents one of the few examples of a positively charged species to exhibit a propensity for the air-water interface. As such, these results expand on the growing body of work on specific ion adsorption.

Modeling ethanol/water adsorption in all-silica zeolites using the real adsorbed solution theory

A comprehensive set of single-component and binary isotherms were collected for ethanol/water adsorption into the siliceous forms of 185 known zeolites using grand-canonical Monte Carlo simulations. Using these data, a systematic analysis of ideal/real adsorbed-solution theory (IAST/RAST) was conducted and activity coefficients were derived for ethanol/water mixtures adsorbed in different zeolites based on RAST. It was found that activity coefficients of ethanol are close to unity while activity coefficients of water are larger in most zeolites, indicating a positive excess free energy of the mixture. This observation can be attributed to water/ethanol interactions being less favorable than water/water interactions in the single-component adsorption of water at comparable loadings. The deviation from ideal behavior can be highly structure-dependent but no clear correlation with pore diameters was identified. Our analysis also demonstrates the following: (1) accurate unary isotherms in the low-loading regime are critical for obtaining physically sensible activity coefficients; (2) the global regression scheme to solve for activity model parameters performs better than fitting activity models to activity coefficients calculated locally at each binary state point; and (3) including the dependence on adsorption potential offers only a minor benefit for describing binary adsorption at the lowest fugacities. Finally, the Margules activity model was found incapable of capturing the non-ideal adsorption behavior over the entire range of fugacities and compositions in all zeolites, but for conditions typical of solution-phase adsorption, RAST predictions using zeolite-specific or even bulk Margules parameters provide an improved description compared to IAST.

The ecdysone-induced bZIP transcription factor MafB establishes a positive feedback loop to enhance vitellogenesis and reproduction in the <i>Aedes aegypti</i> mosquito

Female mosquitoes require a vertebrate blood meal to activate reproduction, transmitting numerous devastating human diseases. Vitellogenesis is a central event of female reproduction that involves the massive production of vitellogenin (Vg) in the fat body and the maturation of ovaries. This process is controlled by the steroid hormone 20-hydroxyecdysone (20E); however, its molecular regulatory basis remains not completely understood. We found that the expression of Aedes aegypti muscle aponeurosis fibromatosis B ( AaMafB ), coding for a basic leucine zipper (bZIP) transcription factor, was significantly up-regulated after a blood meal. The 20E-bound ecdysone receptor–ultraspiracle heterodimer directly targeted the ecdysone response element in the promoter of AaMafB , activating its transcription. Coimmunoprecipitation assays illustrated the interaction between Aa MafB and Cap “n” collar C ( Aa CncC), another bZIP transcription factor. RNA interference–mediated depletion of Aa MafB or Aa CncC led to impaired ovarian growth, decreased expression of AaVg and Halloween genes, and reduced 20E levels. The Aa MafB– Aa CncC heterodimer directly activated the transcription of AaVg and AaShade by targeting the antioxidant response element in their promoters. Together, our results indicate that AaMafB functions as an early 20E response gene, the product of which heterodimerizes with Aa CncC to maintain high 20E levels and facilitates activation of AaVg in mosquitoes after a blood meal.

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Heterogeneous dynamics in aging phosphate-based geopolymer

The time-evolution of dynamics as well as microstructure and mechanical response of phosphate-based geopolymers was probed using x-ray photon correlation spectroscopy and rheological tests. The analyzed relaxation processes in the freshly prepared geopolymer mixes evidenced a q-independent mode of the autocorrelation function, ascribed to density fluctuations of the already established molecular network, undergoing reconfiguration without significant mass transport. Upon curing, the detected motions are localized and depict a system evolving toward structural arrest dominated by slower hyperdiffusive dynamics, characterized by a compressed exponential regime, pointing to a structural relaxation process subjected to internal stresses, in a context of marked dynamical and structural heterogeneity. The system ages through a “densification” process producing declining small angle scattered intensity, as two finely intermixed gel-like reaction products, namely, one hydrated aluminophosphate and one hydrated silica, form a percolated network possessing surface fractal scaling of progressively shorter average correlation length. In this scenario, the nominal Al/P molar ratio of the mix, being an index of network-forming ability, is positively correlated with the dynamic viscosity and the overall kinetics, whereas the contrary occurs for the fraction of water.

An RNase III–processed sRNA coordinates sialic acid metabolism of <i>Salmonella enterica</i> during gut colonization

Sialic acids derived from colonic mucin glycans are crucial nutrients for enteric bacterial pathogens like Salmonella . The uptake and utilization of sialic acid in Salmonella depend on coordinated regulons, each activated by specific metabolites at the transcriptional level. However, the mechanisms enabling crosstalk among these regulatory circuits to synchronize gene expression remain poorly understood. Here, we identify ManS, a small noncoding RNA derived from the 3’ UTR of STM1128 mRNA transcribed from a Salmonella enterica –specific genetic locus, as an important posttranscriptional regulator coordinating sialic acid metabolism regulons. ManS is primarily processed by RNase III and, along with its parental transcripts, is specifically activated by N-acetylmannosamine (ManNAc), the initial degradation product of sialic acid. We found that the imperfect stem-loop structure at the 5’ end of ManS allows RNase III to cleave in a noncanonical manner, generating two functional types of ManS with the assistance of RNase E and other RNases: short isoforms with a single seed region that regulate the uptake of N-acetylglucosamine, an essential intermediate in sialic acid metabolism; and long isoforms with an additional seed region that regulate multiple genes involved in central and secondary metabolism. This sophisticated regulation by ManS significantly impacts ManNAc metabolism and S. enterica ’s competitive behavior during infection. Our findings highlight the role of sRNA in coordinating transcriptional circuits and advance our understanding of RNase III-mediated processing of 3’ UTR-derived sRNAs, underscoring the important role of ManNAc in Salmonella adaptation within host environments.

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Phase boundaries promote chemical reactions through localized fluxes

One of the hypothesized functions of biomolecular condensates is to act as chemical reactors, where chemical reactions can be modulated, i.e., accelerated or slowed down, while substrate molecules enter and products exit from the condensate. Similarly, the components themselves that take part in the architectural integrity of condensates might be modified by active (energy consuming, non-equilibrium) processes, e.g., by ATPase chaperones or by kinases and phosphatases. In this work, we study how the presence of spatial inhomogeneities, such as in the case of liquid–liquid phase separation, affects active chemical reactions and results in the presence of directional flows of matter, which are one of the hallmarks of non-equilibrium processes. We establish the minimal conditions for the existence of such spatial currents, and we furthermore find that these fluxes are maximal at the condensate interface. These results propose that some condensates might be most efficient as chemical factories due to their interfaces rather than their volumes and could suggest a possible biological reason for the observed abundance of small non-fusing condensates inside the cell, thus maximizing their surface and the associated fluxes.

The false evidence rate: An approach to frequentist error rate control conditioning on the observed <i>P</i> value

A P value is conventionally interpreted either as a) the probability by chance of obtaining more extreme results than those observed or b) a tool for declaring significance at a prespecified level. Both approaches carry difficulties: b) does not allow users to make inferences based on the data in hand, and is not rigorously followed by researchers in practice, while (a) is not meaningful as an error rate. Although P values retain an important role, these shortcomings are likely to have contributed significantly to the scientific reproducibility crisis. We introduce the concept of defining long-run frequentist error rates given the observed data, allowing researchers to make accurate and intuitive inferences about the probability of making an error after proposing that the null hypothesis is false. As one approach, we define the false evidence rate (FER) as the probability, under the null hypothesis, of observing a hypothetical future P value providing evidence toward the alternative hypothesis suggested by the observed P value, which we define as a false positive. FERs are much more conservative than their corresponding P values, consistent with studies demonstrating that the latter do not effectively control error rates across the scientific literature. To obtain an FER below 5%, one needs to obtain a P value below approximately 5 × 10 − 5 , while a P value of 5% corresponds to an FER of about 25%.

Atomistic dynamics of elimination and substitution driven by entrance channel

E2 elimination and SN2 substitution reactions are of central importance in preparative organic synthesis due to their stereospecificity. Herein, atomistic dynamics of a prototype reaction of ethyl chloride with hydroxide ion are uncovered that show strikingly distinct features from the case with fluoride anion. Chemical dynamics simulations reproduce the experimental reaction rate and reveal that the E2 proceeding through a direct elimination mechanism dominates over SN2 for the hydroxide ion reaction. This unexpected finding of a pronounced contribution of direct reaction dynamics, even at a near-thermal energy, is in strong contrast to the complex-mediated indirect mechanism for the fluoride case that characterizes the low-energy ion–molecule reactions. The entrance channel structures are found to be crucial and the differences are attributed to subtle changes in the hydrogen-bonding interaction of the approaching reactants. This effect presents in E2/SN2 reactions of different bases and alkyl halides and might play a role in complex chemical networks and environments.

Cluster perturbation theory. XI. Excitation-energy series using a variational excitation-energy function

Traditionally, excitation energies in coupled-cluster (CC) theory have been calculated by solving the CC Jacobian eigenvalue equation. However, based on our recent work [Jørgensen et al., Sci. Adv. 10, eadn3454 (2024)], we propose a reformulation of the calculation of excitation energies where excitation energies are determined as a conventional molecular property. To this end, we introduce an excitation-energy function that depends on the CC Jacobian and the right and left eigenvectors for the Jacobian eigenvalue problem. This excitation-energy function is variational with respect to the right and left eigenvectors but not with respect to the cluster amplitudes. Instead, the cluster amplitudes satisfy the cluster-amplitude equations, and we set up an excitation-energy Lagrangian by adding to the excitation-energy function the cluster-amplitude equations with an undetermined multiplier for each cluster-amplitude constraint. The excitation-energy Lagrangian is variational in all its parameters. Based on the variational property of the Lagrangian, we have determined two quadratically convergent excitation-energy series: the total-order cluster-perturbation (tCP) and variational cluster-perturbation (vCP) excitation-energy series. Calculations of the excitation energies of three small molecules have shown that the vCP series is to be preferred over the tCP series. The test calculations have been carried out for CPS(D) expansions [targeting the CC singles-and-doubles (CCSD) wave function from the CC singles wave function] and the CPSD(T) expansion [targeting the CC singles-doubles-triples (CCSDT) wave function from the CCSD wave function]. For the S(D) and SD(T) orbital excitation space calculations, we obtain in the second vCP iteration excitation energies with a mean deviation from CCSD excitation energies of about 0.04 eV for the S(D) orbital spaces, and for the SD(T) orbital space calculation, we obtain a mean deviation from the CCSDT excitation energies of 0.001 eV.

Molecular engineering charge transfer and triplet exciton formation in donor–acceptor cocrystals

Organic donor–acceptor (D–A) cocrystals are gaining attention for their potential applications in optoelectronic devices. This study explores the dynamics of charge transfer (CT) and triplet exciton formation in various D–A cocrystals. By examining a series of D–A cocrystals composed of coronene (COR), peri-xanthenoxanthene (PXX), and perylene (PER) donors paired with N,N-bis(3′-pentyl)perylene-3,4:9,10-bis(dicarboximide) (PDI), naphthalene-1,4:5,8-tetracarboxy-dianhydride (NDA), or pyrene-4,5,9,10-tetraone (PTO) acceptors, using transient absorption microscopy and time-resolved electron paramagnetic resonance spectroscopy, we find that the strength of the CT interaction influences the nature and yield of triplet excitons produced by CT state recombination. In particular, in the PER-PDI, COR-PTO, and PER-PTO cocrystals, localized triplet excitons are lower in energy than the CT state. By contrast, no localized triplet excitons are available to the CT states of the PXX-NDA, PER-NDA, and PXX-PTO cocrystals, and as a result, the CT states rapidly decay to ground state with no triplet formation. Moreover, density functional theory calculations show that the transition between delocalized CT states to a triplet state localized to a single donor or acceptor unit provides the source of spin–orbit coupling necessary when the triplet states are energetically accessible. These findings provide insights into the design of molecular materials with tailored exciton properties for optoelectronic applications.