Anomalous electrons in a metallic kagome ferromagnet.

Ordinary metals contain electron liquids within well-defined 'Fermi' surfaces at which the electrons behave as if they were non-interacting. In the absence of transitions to entirely new phases such as insulators or superconductors, interactions between electrons induce scattering that is quadratic in the deviation of the binding energy from the Fermi level. A long-standing puzzle is that certain materials do not fit this 'Fermi liquid' description. A common feature is strong interactions between electrons relative to their kinetic energies. One route to this regime is special lattices to reduce the electron kinetic energies. Twisted bilayer graphene1-4 is an example, and trihexagonal tiling lattices (triangular 'kagome'), with all corner sites removed on a 2 × 2 superlattice, can also host narrow electron bands5 for which interaction effects would be enhanced. Here we describe spectroscopy revealing non-Fermi-liquid behaviour for the ferromagnetic kagome metal Fe3Sn2 (ref. 6). We discover three C3-symmetric electron pockets at the Brillouin zone centre, two of which are expected from density functional theory. The third and most sharply defined band emerges at low temperatures and binding energies by means of fractionalization of one of the other two, most likely on the account of enhanced electron-electron interactions owing to a flat band predicted to lie just above the Fermi level. Our discovery opens the topic of how such many-body physics involving flat bands7,8 could differ depending on whether they arise from lattice geometry or from strongly localized atomic orbitals9,10.

Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes.

We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene poor, the mouse MSY is 99.9% euchromatic and contains about 700 protein-coding genes. Only 2% of the MSY derives from the ancestral autosomes that gave rise to the mammalian sex chromosomes. Instead, all but 45 of the MSY's genes belong to three acquired, massively amplified gene families that have no homologs on primate MSYs but do have acquired, amplified homologs on the mouse X chromosome. The complete mouse MSY sequence brings to light dramatic forces in sex chromosome evolution: lineage-specific convergent acquisition and amplification of X-Y gene families, possibly fueled by antagonism between acquired X-Y homologs. The mouse MSY sequence presents opportunities for experimental studies of a sex-specific chromosome in its entirety, in a genetically tractable model organism.

Tunable Magnetism in Atomically Thin Itinerant Antiferromagnet with Room-Temperature Ferromagnetic Order.

Addressing the need for modulated spin configurations is crucial, as they serve as the foundational building blocks for next-generation spintronics, particularly in atomically thin structures and at room temperature. In this work, we realize intrinsic ferromagnetism in monolayer flakes and tunable ferro-/antiferromagnetism in (Fe0.56Co0.44)5GeTe2 antiferromagnets. Remarkably, the ferromagnetic ordering (≥1 L) and antiferromagnetic ordering (≥4 L) remain discernible up to room temperature. The TC (∼310 K) of the monolayer flakes sets a record high for known exfoliated monolayer van der Waals magnets. Within the framework of A-type antiferromagnetism, a notable odd-even layer-number effect at elevated temperatures (T = 150 K) is observed. Of particular interest is the strong ferromagnetic order in even-layer flakes at low temperatures. The intricate interplay among magnetic field strength, layer number, and temperature gives rise to a diverse array of phenomena, holding promise not only for new physics but also for practical applications.

Meioc maintains an extended meiotic prophase I in mice.

The meiosis-specific chromosomal events of homolog pairing, synapsis, and recombination occur over an extended meiotic prophase I that is many times longer than prophase of mitosis. Here we show that, in mice, maintenance of an extended meiotic prophase I requires the gene Meioc, a germ-cell specific factor conserved in most metazoans. In mice, Meioc is expressed in male and female germ cells upon initiation of and throughout meiotic prophase I. Mouse germ cells lacking Meioc initiate meiosis: they undergo pre-meiotic DNA replication, they express proteins involved in synapsis and recombination, and a subset of cells progress as far as the zygotene stage of prophase I. However, cells in early meiotic prophase-as early as the preleptotene stage-proceed to condense their chromosomes and assemble a spindle, as if having progressed to metaphase. Meioc-deficient spermatocytes that have initiated synapsis mis-express CYCLIN A2, which is normally expressed in mitotic spermatogonia, suggesting a failure to properly transition to a meiotic cell cycle program. MEIOC interacts with YTHDC2, and the two proteins pull-down an overlapping set of mitosis-associated transcripts. We conclude that when the meiotic chromosomal program is initiated, Meioc is simultaneously induced so as to extend meiotic prophase. Specifically, MEIOC, together with YTHDC2, promotes a meiotic (as opposed to mitotic) cell cycle program via post-transcriptional control of their target transcripts.

A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary.

The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary. By profiling gene expression in the mouse fetal ovary in mutants with whole tissue and single-cell techniques, we identified 104 genes expressed specifically in pre-meiotic to pachytene germ cells. We characterized the regulation of these genes by 1) retinoic acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, a downstream target of RA required for the chromosomal program of meiotic prophase. Initial induction of practically all identified meiotic prophase genes requires Dazl. In the presence of Dazl, RA induces at least two pathways: one Stra8-independent, and one Stra8-dependent. Genes vary in their induction by Stra8, spanning fully Stra8-independent, partially Stra8-independent, and fully Stra8-dependent. Thus, Stra8 regulates the entirety of the chromosomal program but plays a more nuanced role in governing the gene expression program. We propose that Stra8-independent gene expression enables the stockpiling of selected meiotic structural proteins prior to the commencement of the chromosomal program. Unexpectedly, we discovered that Stra8 is required for prompt down-regulation of itself and Rec8. Germ cells that have expressed and down-regulated Stra8 are refractory to further Stra8 expression. Negative feedback of Stra8, and subsequent resistance to further Stra8 expression, may ensure a single, restricted pulse of Stra8 expression. Collectively, our findings reveal a gene regulatory logic by which germ cells prepare for the chromosomal program of meiotic prophase, and ensure that it is induced only once.

Licensing of primordial germ cells for gametogenesis depends on genital ridge signaling.

In mouse embryos at mid-gestation, primordial germ cells (PGCs) undergo licensing to become gametogenesis-competent cells (GCCs), gaining the capacity for meiotic initiation and sexual differentiation. GCCs then initiate either oogenesis or spermatogenesis in response to gonadal cues. Germ cell licensing has been considered to be a cell-autonomous and gonad-independent event, based on observations that some PGCs, having migrated not to the gonad but to the adrenal gland, nonetheless enter meiosis in a time frame parallel to ovarian germ cells -- and do so regardless of the sex of the embryo. Here we test the hypothesis that germ cell licensing is cell-autonomous by examining the fate of PGCs in Gata4 conditional mutant (Gata4 cKO) mouse embryos. Gata4, which is expressed only in somatic cells, is known to be required for genital ridge initiation. PGCs in Gata4 cKO mutants migrated to the area where the genital ridge, the precursor of the gonad, would ordinarily be formed. However, these germ cells did not undergo licensing and instead retained characteristics of PGCs. Our results indicate that licensing is not purely cell-autonomous but is induced by the somatic genital ridge.

Retinoic acid activates two pathways required for meiosis in mice.

In all sexually reproducing organisms, cells of the germ line must transition from mitosis to meiosis. In mice, retinoic acid (RA), the extrinsic signal for meiotic initiation, activates transcription of Stra8, which is required for meiotic DNA replication and the subsequent processes of meiotic prophase. Here we report that RA also activates transcription of Rec8, which encodes a component of the cohesin complex that accumulates during meiotic S phase, and which is essential for chromosome synapsis and segregation. This RA induction of Rec8 occurs in parallel with the induction of Stra8, and independently of Stra8 function, and it is conserved between the sexes. Further, RA induction of Rec8, like that of Stra8, requires the germ-cell-intrinsic competence factor Dazl. Our findings strengthen the importance of RA and Dazl in the meiotic transition, provide important details about the Stra8 pathway, and open avenues to investigate early meiosis through analysis of Rec8 induction and function.

Charge fluctuations in the intermediate-valence ground state of SmCoIn5.

The microscopic mechanism of heavy band formation, relevant for unconventional superconductivity in CeCoIn5 and other Ce-based heavy fermion materials, depends strongly on the efficiency with which f electrons are delocalized from the rare earth sites and participate in a Kondo lattice. Replacing Ce3+ (4f1, J = 5/2) with Sm3+ (4f5, J = 5/2), we show that a combination of the crystal electric field and on-site Coulomb repulsion causes SmCoIn5 to exhibit a Γ7 ground state similar to CeCoIn5 with multiple f electrons. We show that with this single-ion ground state, SmCoIn5 exhibits a temperature-induced valence crossover consistent with a Kondo scenario, leading to increased delocalization of f holes below a temperature scale set by the crystal field, Tv ≈ 60 K. Our result provides evidence that in the case of many f electrons, the crystal field remains the dominant tuning knob in controlling the efficiency of delocalization near a heavy fermion quantum critical point, and additionally clarifies that charge fluctuations play a general role in the ground state of "115" materials.

Comprehensive Profiling of Mutations to Influenza Virus PB2 That Confer Resistance to the Cap-Binding Inhibitor Pimodivir.

Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.

Two-dimensional characterization of three-dimensional magnetic bubbles in Fe3Sn2 nanostructures.

We report differential phase contrast scanning transmission electron microscopy (TEM) of nanoscale magnetic objects in Kagome ferromagnet Fe3Sn2 nanostructures. This technique can directly detect the deflection angle of a focused electron beam, thus allowing clear identification of the real magnetic structures of two magnetic objects including three-ring and complex arch-shaped vortices in Fe3Sn2 by Lorentz-TEM imaging. Numerical calculations based on real material-specific parameters well reproduced the experimental results, showing that the magnetic objects can be attributed to integral magnetizations of two types of complex three-dimensional (3D) magnetic bubbles with depth-modulated spin twisting. Magnetic configurations obtained using the high-resolution TEM are generally considered as two-dimensional (2D) magnetic objects previously. Our results imply the importance of the integral magnetizations of underestimated 3D magnetic structures in 2D TEM magnetic characterizations.

A reconfigurable optofluidic Michelson interferometer using tunable droplet grating.

This paper presents a novel optofluidic Michelson interferometer based on droplet microfluidics used to create a droplet grating. The droplet grating is formed by a stream of plugs in the microchannel with constant refractive index variation. It has a real-time tunability in the grating period through varying the flow rates of the liquids and index variation via different combinations of liquids. The optofluidic Michelson interferometer is highly sensitive and is suitable for the measurement of biomedical and biochemical buffer solutions. The experimental results show that it has a sensitivity of 66.7 nm per refractive index unit (RIU) and a detection range of 0.086 RIU.

Fuchs endothelial corneal dystrophy and corneal endothelial diseases: East meets West.

Fuchs endothelial corneal dystrophy (FECD) is amongst one of the most common indications for endothelial keratoplasty worldwide. Despite being originally described among Caucasians, it is now known to be prevalent among a large number of populations, including Asians. While the FECD phenotype is classically described as that of central guttate and pigment deposits associated with corneal endothelial dysfunction, there are subtle yet important differences in how FECD and its phenocopies may present in Caucasians vs Asians. Such differences are paralled by genotypic variations and disease management preferences which appear to be geographically and ethnically delineated. This article provides a succinct review of such differences, with a focus on diagnostic and management issues which may be encountered by ophthalmologists practicing in the different geographic regions, when evaluating a patient with FECD.

Identification of soluble microbial products (SMPs) from the fermentation and methanogenic phases of anaerobic digestion.

The production and transformation of Soluble Microbial Products (SMPs) in biological treatment systems is complex, and their genesis and reasons for production are still unclear. SMPs are important since they constitute the main fraction of effluent COD (both aerobic and anaerobic), and hence are the main precursors for disinfection by-products (DBPs). In addition, they are a key component of fouling in membrane bioreactors. Hence, it is important to identify the chemical composition of SMPs, determine their origin, and understand what system parameters influence their production so we can possibly develop strategies to control their production. This study focuses on the production and identification of SMPs in an anaerobic batch process being fed a synthetic feed. To further understand the origins of SMPs, and how they are produced, we analysed the processes of fermentation and methanogenesis independently which has never been done in detail before. SMP concentration, molecular weight distribution and carbohydrate analyses were used to estimate the amount of SMPs in the supernatants. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-Time-of-Flight mass spectrometry (LC-ESI-Q-ToF) were used to identify many of the SMPs which have relative masses up to 2 kDa. Our results showed that fermentation released much higher SMP concentrations compared to methanogenesis, especially in the range of 70 k-1000 k Da and 106-1500 Da. Alkanes, alkenes, alcohols, acids, and nitrogen-compounds were the major group of compounds identified in the supernatant of both fermentation and methanogenesis, and 71% of the compounds identified were found in both phases of digestion. Results from LC-ESI-Q-ToF analysis identified components of the cell membrane, such as phosphatidylglycerol, phosphatidylethanolamine and phosphatidylserine, as well as other compounds such as flavonoids, acylglycerol, terpene and terpenoids, benzenoid, glyceride, steroid and steroid derivatives.

Target Bubbles in Fe3Sn2 Nanodisks at Zero Magnetic Field.

We report a vortex-like magnetic configuration in uniaxial ferromagnet Fe3Sn2 nanodisks using differential phase contrast scanning transmission electron microscopy. This magnetic configuration is transferred from a conventional magnetic vortex using a zero-magnetic-field warming process and is characterized by a series of concentric cylinder domains. We termed them as "target bubbles" that are identified as three-dimensional depth-modulated magnetic objects in combination with numerical simulations. Target bubbles have room-temperature stability even at zero magnetic field and multiple stable magnetic configurations. These advantages render the target bubble an ideal bit to be an information carrier and can advance magnetic target bubbles toward functionalities in the long term by incorporating emergent degrees of freedom and purely electrically controllable magnetism.

Facilitators and Barriers to Post-partum Diabetes Screening Among Mothers With a History of Gestational Diabetes Mellitus-A Qualitative Study From Singapore.

Introduction: Gestational Diabetes Mellitus (GDM) affects one in six births worldwide. Mothers with GDM have an increased risk of developing post-partum Type-2 Diabetes Mellitus (T2DM). However, their uptake of post-partum diabetes screening is suboptimal, including those in Singapore. Literature reports that the patient-doctor relationship, mothers' concerns about diabetes, and family-related practicalities are key factors influencing the uptake of such screening. However, we postulate additional factors related to local society, healthcare system, and policies in influencing post-partum diabetes screening among mothers with GDM. Aim: The qualitative research study aimed to explore the facilitators and barriers to post-partum diabetes screening among mothers with GDM in an Asian community. Methods: In-depth interviews were carried out on mothers with GDM at a public primary care clinic in Singapore. Mothers were recruited from those who brought their child for vaccination appointments and their informed consent was obtained. Both mothers who completed post-partum diabetes screening within 12 weeks after childbirth and those who did not were purposively recruited. The social ecological model (SEM) provides the theoretical framework to identify facilitators and barriers at the individual, interpersonal, organizational, and policy levels. Results: Twenty multi-ethnic Asian mothers with GDM were interviewed. At the individual and interpersonal level, self-perceived risk of developing T2DM, understanding the need for screening and the benefits of early diagnosis, availability of confinement nanny in Chinese family, alternate caregivers, emotional, and peer support facilitated post-partum diabetes screening. Barriers included fear of the diagnosis and its consequences, preference for personal attention and care to child, failure to find trusted caregiver, competing priorities, and unpleasant experiences with the oral glucose tolerance test. At the organizational and public policy level, bundling of scheduled appointments, and standardization of procedure eased screening but uptake was hindered by inconvenient testing locations, variable post-partum care practices and advice in the recommendations for diabetes screening. Conclusion: Based on the SEM, facilitators and barriers towards post-partum diabetes screening exist at multiple levels, with some contextualized to local factors. Interventions to improve its uptake should be multi-pronged, targeting not only at personal but also familial, health system, and policy factors to ensure higher level of success.

Comparison of Pre-Treatment vs. Post-Treatment Retinal Vessel Density in Children with Amblyopia.

BACKGROUND: Prior studies have reported a lower retinal vessel density (RVD) in amblyopic vs. non-amblyopic eyes. No studies have shown if amblyopic eye RVD changes following patching therapy. We assessed for RVD differences between pre-treatment vs. post-treatment amblyopic eyes. METHODS: Participants were included if they were <10 years old with unilateral amblyopia. All subjects were required to visit the pediatric eye clinic for examination. Exclusion criteria included: deprivation amblyopia, bilateral amblyopia, nystagmus, media opacity, intraocular inflammation, or any retinal disease. All participants underwent optical coherence tomography angiography (OCTA) before and after refraction and patching treatment. Outcomes included superficial (SCP) and deep (DCP) capillary plexus RVD. RESULTS: 12 patients (12 amblyopic eyes) were included. Mean (SD) age, gestational age (GA), birth weight (BW), and follow-up time were: 6.5 (1.7) years, 39.4 weeks (1.4 w), 3271 g (262 g), and 114 days (46d), respectively. There was a significant increase in the RVD of the DCP in 3 × 3-mm scans after treatment, specifically in the whole image (52.6 ± 5.75 vs 56.5 ± 2.48%, p = .046) and superior hemisphere regions (52.47 ± 6.17 vs 56.73 ± 2.27%, p = .048). CONCLUSIONS: Amblyopic eye RVD potentially increases after amblyopia treatment in specific regions of the retina. Further research is required to refine this clinical parameter.

An improved dynamic model of tuning fork probe for scanning probe microscopy.

This paper presents a two coupled oscillators model to describe the dynamics of a tuning fork with a probe attached. The two coupled oscillators are unbalanced only in their effective masses and the damping ratios. By applying a frequency domain system identification approach in experimental investigation of various probe attachment cases, a good accuracy of the model is demonstrated. The effectiveness of the model is further demonstrated in quantitative analysis of the noise performance and the sensitivity of force sensing with a tuning fork probe. Compared with existing models, the proposed model can more accurately characterize the dynamics of a tuning fork probe.

Rapid degradation of hypoxia-inducible factor-1alpha by KRH102053, a new activator of prolyl hydroxylase 2.

BACKGROUND AND PURPOSE: Hypoxia-inducible factor (HIF) is a transcription factor induced by hypoxia and degraded by ubiquitin-dependent proteasomes in normoxic conditions. Under hypoxic conditions, hydroxylation of HIF-1alpha subunit by prolyl hydroxylase (PHD) is suppressed, thus leading to increased levels of HIF. Although PHD2 plays a key role in regulating the levels of HIF, chemical activators of PHD2 are relatively unknown. The aim of this study was to identify small molecule activators of PHD2 that could be used, eventually, to suppress the level of HIF-1alpha. EXPERIMENTAL APPROACH: By using the overproduced PHD2 as a target, a molecular library consisting of more than 600 small molecules with a benzopyran structure was screened with an HPLC assay method. KEY RESULTS: We found a potent activator of PHD2, KRH102053 (2-amino-4-methylsulphanyl-butylic acid-4-methoxy-6-(4-methoxy-benzylamino)-2,2-dimethyl-chroman-3-yl ester). The effects of KRH102053 on controlling HIF were studied in human HOS osteosarcoma, rat PC12 phaeochromocytoma and human HepG2 hepatoma cells. Under our experimental conditions, KRH102053 decreased the protein level of HIF-1alpha and the mRNA levels of HIF-regulated downstream target genes, such as vascular endothelial growth factor, aldolase A, enolase 1 and monocarboxylate transporter 4. Consistent with these results, KRH102053 also inhibited the rates of HIF-related migration and invasion of HOS cells as well as the degree of tube formation in human umbilical vein endothelium cells. CONCLUSIONS AND IMPLICATIONS: These results suggest that KRH102053 and its structural analogues have the potential for use as therapeutic agents against various diseases associated with HIF.

Nuclear localisation of glutathione S-transferase pi is an evaluation factor for drug resistance in gynaecological cancers.

AIMS: Nuclear glutathione S-transferase pi (GST7pi) has been reported to protect cancer cells against anticancer drugs. The aim of the present study was to evaluate the clinical significance of nuclear GSTpi in gynaecological cancer. MATERIALS AND METHODS: We carried out an immunohistochemical analysis of GSTpi, and examined the correlation between nuclear GSTpi: expression and prognosis in 43 epithelial ovarian cancers. We compared expression levels before and after chemotherapy in uterine cervical cancers and endometrial cancers. RESULTS: The 5-year progression-free survival rate of the nuclear GSTpi-positive group was lower than that of the cytoplasmic GSTpi-positive group, and was significantly lower than that of the negative group (14.3% vs 34.8% vs 66.7%; P = 0.041). The expression of nuclear GSTpi was compared before and after chemotherapy in uterine cervical and endometrial cancers. In eight out of 12 cases (66.7%), the expression turned positive after the chemotherapy. CONCLUSIONS: We suggest that nuclear localisation of GSTpi is associated with drug resistance. The nuclear localisation of GSTpi in tumour cells is a useful prognosticator, and may contribute to the selection of anticancer drugs for gynaecological cancers.