Quantitative study of birefringence effects in fiber-based orthogonal-pump FWM systems.

Optical fibers have unwanted residual birefringence due to imperfections in fabrication processes and environmental conditions. This birefringence will randomize the state of polarization of propagating signals and may harm the performance of four-wave mixing based processing devices. Here, we present a quantitative study of the effects of birefringence in orthogonal-pump four-wave mixing systems, and identify different regions of operation of the optical fiber, mainly determined by the relative magnitude between the physical length L and beat length Lb. This finding clarifies the characteristics of the complex interplay between birefringence and four-wave mixing and advises appropriate fiber length selection for minimized polarization dependent gain.

Fabrication and mechanical characterization of hydrogel-based 3D cell-like structures.

In this article, we demonstrate the fabrication of 3D cell-like structures using a femtosecond laser-based two-photon polymerization technique. By employing poly(ethylene glycol) diacrylate monomers as a precursor solution, we fabricate 3D hemispheres that resemble morphological and biomechanical characteristics of natural cells. We employ an optical tweezers-based microrheology technique to measure the viscoelastic properties of the precursor solutions inside and outside the structures. In addition, we demonstrate the interchangeability of the precursor solution within fabricated structures without impairing the microstructures. The combination of two-photon polymerization and microrheological measurements by optical tweezers demonstrated here represents a powerful toolbox for future investigations into cell mimic and artificial cell studies.

Global climate change, diet, and the complex relationship between human host and microbiome: Towards an integrated picture.

Dietary changes can alter the human microbiome with potential detrimental consequences for health. Given that environment, health, and evolution are interconnected, we ask: Could diet-driven microbiome perturbations have consequences that extend beyond their immediate impact on human health? We address this question in the context of the urgent health challenges posed by global climate change. Drawing on recent studies, we propose that not only can diet-driven microbiome changes lead to dysbiosis, they can also shape life-history traits and fuel human evolution. We posit that dietary shifts prompt mismatched microbiome-host genetics configurations that modulate human longevity and reproductive success. These mismatches can also induce a heritable intra-holobiont stress response, which encourages the holobiont to re-establish equilibrium within the changed nutritional environment. Thus, while mismatches between climate change-related genetic and epigenetic configurations within the holobiont increase the risk and severity of diseases, they may also affect life-history traits and facilitate adaptive responses. These propositions form a framework that can help systematize and address climate-related dietary challenges for policy and health interventions.

Environmentally induced plasticity of programmed DNA elimination boosts somatic variability in Paramecium tetraurelia.

Can ecological changes impact somatic genome development? Efforts to resolve this question could reveal a direct link between environmental changes and somatic variability, potentially illuminating our understanding of how variation can surface from a single genotype under stress. Here, we tackle this question by leveraging the biological properties of ciliates. When Paramecium tetraurelia reproduces sexually, its polyploid somatic genome regenerates from the germline genome through a developmental process that involves the removal of thousands of ORF-interrupting sequences known as internal eliminated sequences (IESs). We show that exposure to nonstandard culture temperatures impacts the efficiency of this process of programmed DNA elimination, prompting the emergence of hundreds of incompletely excised IESs in the newly developed somatic genome. These alternative DNA isoforms display a patterned genomic topography, impact gene expression, and might be inherited transgenerationally. On this basis, we conclude that environmentally induced developmental thermoplasticity contributes to genotypic diversification in Paramecium.

A Review of Capabilities and Scope for Hybrid Integration Offered by Silicon-Nitride-Based Photonic Integrated Circuits.

In this review we present some of the recent advances in the field of silicon nitride photonic integrated circuits. The review focuses on the material deposition techniques currently available, illustrating the capabilities of each technique. The review then expands on the functionalisation of the platform to achieve nonlinear processing, optical modulation, nonvolatile optical memories and integration with III-V materials to obtain lasing or gain capabilities.

Yield stress "in a flash": investigation of nonlinearity and yielding in soft materials with an optofluidic microrheometer.

Yield stress materials deform as elastic solids or flow as viscous liquids, depending on the applied stress, which also allows them to trap particles below a certain size or density threshold. To investigate the conditions for such a transition at the microscale, we use an optofluidic microrheometer, based on the scattering of an infrared beam onto a microbead, which reaches forces in the nN scale. We perform creep experiments on a model soft material composed of swollen microgels, determining the limits of linear response and yield stress values, and observe quantitative agreement with bulk measurements. However, the motion of the microbead, both below and above yielding, reflects distinctive microscale features of the surrounding material, whose plastic rearrangements were investigated by us using small, passive tracers.

Insulin-like signaling within and beyond metazoans.

Insulin signaling is pivotal in controlling animals' lifespan and responses to environmental changes and, when altered, it may lead to pathogenic states. Despite its importance and relevance for biomedical research, insulin's mechanism of action and the full range of its pathophysiological effects remain incompletely understood. Likewise, the evolutionary origin of insulin and its associated signaling components are unclear. Notwithstanding the common view that insulin signaling originated within metazoans, experimental evidence from non-metazoans suggest a more widespread distribution across eukaryotes. Here, we summarize this evidence. Furthermore, we put forward an evolutionary account that reconciles seemingly contradictory results in the literature.

Newtonian to non-newtonian fluid transition of a model transient network.

The viscosity of gel-forming fluids is notoriously complex and its study can benefit from new model systems that enable a detailed control of the network features. Here we use a novel and simple microfluidic-based active microrheology approach to study the transition from Newtonian to non-Newtonian behavior in a DNA hydrogel whose structure, connectivity, density of bonds, bond energy and kinetics are strongly temperature dependent and well known. In a temperature range of 15 °C, the system reversibly and continuously transforms from a Newtonian dispersion of low-valence nanocolloids into a strongly shear-thinning fluid, passing through a set of intermediate states where it behaves as a power-law fluid. We demonstrate that the knowledge of network topology and bond free energy enables to quantitatively predict the observed behavior using established rheology models.

Group-velocity dispersion in SOI-based channel waveguides with reduced-height.

We report on the experimental characterization, in the telecom C-band, of group-velocity dispersion (D) in 100-nm high rectangular strip waveguides realized by silicon-on-insulator technology. We compare the experimental results with numerical predictions, showing that 100-nm high waveguides exhibit normal dispersion and that the absolute value of the dispersion coefficient D decreases as the waveguide width is increased. D at 1550 nm varies from -8130 to -3900 ps/(nm·km) by increasing the waveguide width from 500 to 800 nm.

Highly efficient dual-level grating couplers for silicon nitride photonics.

We propose and numerically demonstrate a versatile strategy that allows designing highly efficient dual-level grating couplers in different silicon nitride-based photonic platforms. The proposed technique, which can generally be applied to an arbitrary silicon nitride film thickness, is based on the simultaneous optimization of two grating coupler levels to obtain high directionality and grating-fibre mode matching at the same time. This is achieved thanks to the use of two different linear apodizations, with opposite signs, applied to the two grating levels, whose design parameters are determined by using a particle swarm optimization method. Numerical simulations were carried out considering different silicon nitride platforms with 150, 300, 400 and 500 nm thicknesses and initially employing silicon as the material for the top level grating coupler. The use of Si-rich silicon nitride with a refractive index in the range 2.7-3.3 for the top layer material enabled to obtain similar performance (coupling efficiency exceeding - 0.45 dB for the 400 nm thick silicon nitride platform) with relaxed fabrication tolerances. To the best of our knowledge, these numerical results represent the best performance ever reported in the literature for silicon nitride grating couplers without the use of any back-reflector.

Polarization Control in Integrated Silicon Waveguides Using Semiconductor Nanowires.

In this work, we show the design of a silicon photonic-based polarization converting device based on the integration of semiconduction InP nanowires on the silicon photonic platform. We present a comprehensive numerical analysis showing that full polarization conversion (from quasi-TE modes to quasi-TM modes, and vice versa) can be achieved in devices exhibiting small footprints (total device lengths below 20 µm) with minimal power loss (<2 dB). The approach described in this work can pave the way to the realization of complex and re-configurable photonic processors based on the manipulation of the state of polarization of guided light beams.

Long-Term Cardiovascular Outcome in Children with MIS-C Linked to SARS-CoV-2 Infection-An Italian Multicenter Experience.

MIS-C is a multisystem inflammatory syndrome that is characterized by multi-organ failure and cardiac involvement. The aim of this study was to describe the long-term cardiovascular outcome in a cohort of MIS-C pediatric patients, who were admitted to two Italian Pediatric Referral Centers. Sixty-seven patients (mean age 8.7 ± 4.7 years, male 60%) were included; 65 (97%) of them showed cardiac involvement. All of the patients completed one month of the follow-up, and 47% completed 1 year of it. ECG abnormalities were present in 65% of them, arrhythmias were present in 9% of them during an acute phase and it disappeared at the point of discharge or later. Pericarditis were detected in 66% of them and disappeared after 6 months. Coronaritis was observed in 35% of the children during an acute phase, and there were no more instances at the 1-year point. An LV dysfunction was present in 65% of the patients at the beginning of the study, with them having a full recovery at the point of discharge and thereafter. Elevated values of the NTproBNP and hsTp were initially detected, which progressively decreased and normalized at the points of discharge and FU. The CMR at the point of FU, there was a presence of long-term myocardial scars in 50% of the patients that were tested. No deaths that were caused by MIS-C during the FU were recorded. Cardiac involvement in MIS-C patients is almost the rule, but the patients' clinical course was satisfactory, and no additional events or sequelae were observed apart from there being long-term myocardial scars in 50% of the patients that underwent CMR.

Polarization Control in Integrated Graphene-Silicon Quantum Photonics Waveguides.

We numerically investigated the use of graphene nanoribbons placed on top of silicon-on-insulator (SOI) strip waveguides for light polarization control in silicon photonic-integrated waveguides. We found that two factors mainly affected the polarization control: the graphene chemical potential and the geometrical parameters of the waveguide, such as the waveguide and nanoribbon widths and distance. We show that the graphene chemical potential influences both TE and TM polarizations almost in the same way, while the waveguide width tapering enables both TE-pass and TM-pass polarizing functionalities. Overall, by increasing the oxide spacer thickness between the silicon waveguide and the top graphene layer, the device insertion losses can be reduced, while preserving a high polarization extinction ratio.

One Cell, Two Gears: Extensive Somatic Genome Plasticity Accompanies High Germline Genome Stability in Paramecium.

Mutation accumulation (MA) experiments are conventionally employed to study spontaneous germline mutations. However, MA experiments can also shed light on somatic genome plasticity in a habitual and genetic drift-maximizing environment. Here, we revisit an MA experiment that uncovered extraordinary germline genome stability in Paramecium tetraurelia, a single-celled eukaryote with nuclear dimorphism. Our re-examination of isogenic P. tetraurelia MA lines propagated in nutrient-rich medium for >40 sexual cycles reveals that their polyploid somatic genome accrued hundreds of intervening DNA segments (IESs), which are normally eliminated during germline-soma differentiation. These IESs frequently occupy a fraction of the somatic DNA copies of a given locus, producing IES excision/retention polymorphisms, and preferentially fall into a class of epigenetically controlled sequences. Relative to control lines, retained IESs are flanked by stronger cis-acting signals and interrupt an excess of highly expressed coding exons. These findings suggest that P. tetraurelia's elevated germline DNA replication fidelity is associated with pervasive somatic genome plasticity. They show that MA regimes are powerful tools for investigating the role that developmental plasticity, somatic mutations, and epimutations have in ecology and evolution.

Fifty Generations of Amitosis: Tracing Asymmetric Allele Segregation in Polyploid Cells with Single-Cell DNA Sequencing.

Amitosis is a widespread form of unbalanced nuclear division whose biomedical and evolutionary significance remain unclear. Traditionally, insights into the genetics of amitosis have been gleaned by assessing the rate of phenotypic assortment. Though powerful, this experimental approach relies on the availability of phenotypic markers. Leveraging Paramecium tetraurelia, a unicellular eukaryote with nuclear dualism and a highly polyploid somatic nucleus, we probe the limits of single-cell whole-genome sequencing to study the consequences of amitosis. To this end, we first evaluate the suitability of single-cell sequencing to study the AT-rich genome of P. tetraurelia, focusing on common sources of genome representation bias. We then asked: can alternative rearrangements of a given locus eventually assort after a number of amitotic divisions? To address this question, we track somatic assortment of developmentally acquired Internal Eliminated Sequences (IESs) up to 50 amitotic divisions post self-fertilization. To further strengthen our observations, we contrast empirical estimates of IES retention levels with in silico predictions obtained through mathematical modeling. In agreement with theoretical expectations, our empirical findings are consistent with a mild increase in variation of IES retention levels across successive amitotic divisions of the macronucleus. The modest levels of somatic assortment in P. tetraurelia suggest that IESs retention levels are largely sculpted at the time of macronuclear development, and remain fairly stable during vegetative growth. In forgoing the requirement for phenotypic assortment, our approach can be applied to a wide variety of amitotic species and could facilitate the identification of environmental and genetic factors affecting amitosis.

Multi-frequency passive and active microrheology with optical tweezers.

Optical tweezers have attracted significant attention for microrheological applications, due to the possibility of investigating viscoelastic properties in vivo which are strongly related to the health status and development of biological specimens. In order to use optical tweezers as a microrheological tool, an exact force calibration in the complex system under investigation is required. One of the most promising techniques for optical tweezers calibration in a viscoelastic medium is the so-called active-passive calibration, which allows determining both the trap stiffness and microrheological properties of the medium with the least a-priori knowledge in comparison to the other methods. In this manuscript, we develop an optimization of the active-passive calibration technique performed with a sample stage driving, whose implementation is more straightforward with respect to standard laser driving where two different laser beams are required. We performed microrheological measurements over a broad frequency range in a few seconds implementing an accurate multi-frequency driving of the sample stage. The optical tweezers-based microrheometer was first validated by measuring water, and then exemplarily applied to more viscous medium and subsequently to a viscoelastic solution of methylcellulose in water. The described method paves the way to microrheological precision metrology in biological samples with high temporal- and spatial-resolution allowing for investigation of even short time-scale phenomena.

Cross-Generational Effects and Non-random Developmental Response to Temperature Variation in Paramecium.

Unicellular organisms such as ciliates are largely neglected in research on adaptive developmental plasticity, although their nuclear dualism offers ideal circumstances to study development outside an embryonic context. Here, we gain first insights into the ability of the ciliate Paramecium to develop potentially adaptive phenotypic changes in response to early-life adversity. We show that, upon exposure to unconventional culture temperatures, germ line-to-soma differentiation gives rise to coordinated molecular changes that may help attune the number of functional gene copies to the new external conditions. The non-random somatic heterogeneity that developmental plasticity generates is largely epigenetically controlled, shaped by the parental experience, and may prompt a stress response. These findings establish Paramecium as a new model system to study the molecular basis and evolutionary significance of developmental plasticity. In echoing previous indications in mammals, they call for an incorporation of intergenerational effects in adaptation studies.

What's Genetic Variation Got to Do with It? Starvation-Induced Self-Fertilization Enhances Survival in Paramecium.

The pervasiveness of sex despite its well-known costs is a long-standing puzzle in evolutionary biology. Current explanations for the success of sex in nature largely rely on the adaptive significance of the new or rare genotypes that sex may generate. Less explored is the possibility that sex-underlying molecular mechanisms can enhance fitness and convey benefits to the individuals that bear the immediate costs of sex. Here, we show that the molecular environment associated with self-fertilization can increase stress resistance in the ciliate Paramecium tetraurelia. This advantage is independent of new genetic variation, coupled with a reduced nutritional input, and offers fresh insights into the mechanistic origin of sex. In addition to providing evidence that the molecular underpinnings of sexual reproduction and the stress response are linked in P. tetraurelia, these findings supply an integrative explanation for the persistence of self-fertilization in this ciliate.

Integrated Optofluidic Chip for Oscillatory Microrheology.

We propose and demonstrate an on-chip optofluidic device allowing active oscillatory microrheological measurements with sub-µL sample volume, low cost and high flexibility. Thanks to the use of this optofluidic microrheometer it is possible to measure the viscoelastic properties of complex fluids in the frequency range 0.01-10 Hz at different temperatures. The system is based on the optical forces exerted on a microbead by two counterpropagating infrared laser beams. The core elements of the optical part, integrated waveguides and an optical modulator, are fabricated by fs-laser writing on a glass substrate. The system performance is validated by measuring viscoelastic solutions of aqueous worm-like micelles composed by Cetylpyridinium Chloride (CPyCl) and Sodium Salicylate (NaSal).

Separation efficiency maximization in acoustofluidic systems: study of the sample launch-position.

The development of lab-on-chip microfluidic systems based on acoustic actuation, and in particular on the acoustophoretic force, has recently attracted significant attention from the scientific community thanks, in part, to the possibility of sample sorting on the basis of both geometrical and mechanical properties. It is commonly recognized that sample prefocusing and launch-position optimization have a substantial effect on the performance of these systems but a clear explanation of how these two parameters influence the system efficiency is still missing. In this manuscript we discuss the impact of both the sample launch position and the sample distribution at the input by the theoretical analysis of a simplified system and by numerical simulations of realistic configurations. The results show that the system performance can be greatly improved by selecting the proper microchannel dimensions and sample-launch position, offering relevant guidelines for the design of micro-acoustofluidic lab-on-chip devices.