Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased rates of brain protein synthesis during [N1,N2] sleep: L-[1-11C]leucine PET studies in human subjects

During sleep, reduced brain energy demands provide an opportunity for biosynthetic processes like protein synthesis. Sleep is required for some forms of memory consolidation which requires de novo protein synthesis. We measured regional cerebral protein synthesis rates (rCPS) in human subjects to ascertain how rCPS is affected during sleep. Subjects underwent three consecutive L-[1-11C]leucine PET scans with simultaneous polysomnography: 1. rested awake, 2. sleep-deprived awake, 3. sleep. Measured rCPS were similar across the three conditions. Variations in sleep stage times during sleep scans were used to estimate rCPS in sleep stages under the assumption that measured rCPS is the weighted sum of rCPS in each stage, with weights reflecting time and availability of [11C]leucine in that stage. During sleep scans, subjects spent most of the time in N2, N3, and awake and very little time in N1 and REM; rCPS in N1 and REM could not be reliably estimated. When stages N1 and N2 were combined [N1,N2], estimates of rCPS were more robust. In selective regions, estimated rCPS were statistically significantly higher (30–39%) in [N1,N2] compared with N3; estimated rCPS in N3 were similar to values measured in sleep-deprived awake scans. Results indicate increased rates of protein synthesis linked to [N1,N2] sleep.
Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI

Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBVdHb), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO2) in patients with MS (PwMS) and age/sex matched controls. By integrating a flow-diffusion model of oxygen transport, we evaluated the effective oxygen diffusivity of the capillary network (DC) and the partial pressure of oxygen at the mitochondria (PmO2). Significant between-group differences were observed as decreased CBF (p = 0.010), CMRO2 (p < 0.001) and DC (p = 0.002), and increased PmO2 (p = 0.043) in patients compared to controls. No significant differences were observed for CBVdHb (p = 0.389), OEF (p = 0.358), or GM volume (p = 0.302). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS. Our findings may be indicative of reduced oxygen demand or utilisation in the MS brain and mitochondrial dysfunction. Our results suggest changes in brain physiology may precede MRI-detectable GM loss and may contribute to disease progression and neurodegeneration.
Core–shell bioprinting of vascularized in vitro liver sinusoid models

In vitro liver models allow the investigation of the cell behavior in disease conditions or in response to changes in the microenvironment. A major challenge in liver tissue engineering is to mimic the tissue-level complexity: besides the selection of suitable biomaterial(s) replacing the extracellular matrix (ECM) and cell sources, the three-dimensional (3D) microarchitecture defined by the fabrication method is a critical factor to achieve functional constructs. In this study, coaxial extrusion-based 3D bioprinting has been applied to develop a liver sinusoid-like model that consists of a core compartment containing pre-vascular structures and a shell compartment containing hepatocytes. The shell ink was composed of alginate and methylcellulose (algMC), dissolved in human fresh frozen plasma. The algMC blend conferred high printing fidelity and stability to the core–shell constructs and the plasma as biologically active component enhanced viability and supported cluster formation and biomarker expression of HepG2 embedded in the shell. For the core, a natural ECM-like ink based on angiogenesis-supporting collagen-fibrin (CF) matrices was developed; the addition of gelatin (G) enabled 3D printing in combination with the plasma-algMC shell ink. Human endothelial cells, laden in the CFG core ink together with human fibroblasts as supportive cells, formed a pre-vascular network in the core in the absence and presence of HepG2 in the shell. The cellular interactions occurring in the triple culture model enhanced the albumin secretion. In conclusion, core–shell bioprinting was shown to be a valuable tool to study cell–cell-interactions and to develop complex tissue-like models.
Reference genome assembly of the sunburst anemone, Anthopleura sola

Abstract The sunburst anemone Anthopleura sola is an abundant species inhabiting the intertidal zone of coastal California. Historically, this species has extended from Baja California, Mexico to as far north as Monterey Bay, CA. However, recently the geographic range of this species has expanded to Bodega Bay, CA, possibly as far north as Salt Point, CA. This species also forms symbiotic partnerships with the dinoflagellate Breviolum muscatinei, a member of the family Symbiodiniaceae. These partnerships are analogous to those formed between tropical corals and dinoflagellate symbionts, making A. sola an excellent model system to explore how hosts will (co)evolve with novel symbiont populations they encounter as they expand northward. This assembly will serve as the foundation for identifying the population genomic patterns associated with range expansions, and will facilitate future work investigating how hosts and their symbiont partners will evolve to interact with one another as geographic ranges shift due to climate change.
Six new cases of CRB2‐related syndrome and a review of clinical findings in 28 reported patients

The Crumbs homolog‐2 (CRB2)‐related syndrome (CRBS‐RS) is a rarely encountered condition initially described as a triad comprising ventriculomegaly, Finnish nephrosis, and elevated alpha‐fetoprotein levels in maternal serum and amniotic fluid. CRB2‐related syndrome is caused by biallelic, pathogenic variants in the CRB2 gene. Recent reports of CRB2‐RS have highlighted renal disease with persistent proteinuria and steroid‐resistant nephrotic syndrome (SRNS). We report six new and review 28 reported patients with pathogenic variants in CRB2. We compare clinical features and variant information in CRB2 in patients with CRB2‐RS and in those with isolated renal disease. The kidneys were the most frequently involved body system and 11 patients had only renal manifestations with SRNS or nephrotic syndrome. Central nervous system involvement was the next most common manifestation, followed by cardiac findings that included Scimitar syndrome. There was a significant clustering of pathogenic variants for CRB2‐RS in exons 8 and 10, whereas pathogenic variants in exons 12 and 13 were associated with isolated renal disease. Further information is needed to determine optimal management but monitoring for renal and ocular complications should be considered.
The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor–resistant ER+ breast cancer with mitotic aberrations

Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are standard first-line treatments for metastatic ER+ breast cancer. However, acquired resistance to CDK4/6i invariably develops, and the molecular phenotypes and exploitable vulnerabilities associated with resistance are not yet fully characterized. We developed a panel of CDK4/6i-resistant breast cancer cell lines and patient-derived organoids and demonstrate that a subset of resistant models accumulates mitotic segregation errors and micronuclei, displaying increased sensitivity to inhibitors of mitotic checkpoint regulators TTK and Aurora kinase A/B. RB1 loss, a well-recognized mechanism of CDK4/6i resistance, causes such mitotic defects and confers enhanced sensitivity to TTK inhibition. In these models, inhibition of TTK with CFI-402257 induces premature chromosome segregation, leading to excessive mitotic segregation errors, DNA damage, and cell death. These findings nominate the TTK inhibitor CFI-402257 as a therapeutic strategy for a defined subset of ER+ breast cancer patients who develop resistance to CDK4/6i.
From Crisis to Recovery in Korea Strategy, Achievements, and Lessons

This paper reviews and draws lessons from the stabilization and reform program that Korea implemented in response to the 1997-98 crisis. The economy recovered quickly from the deep recession in 1998 and its vulnerability to a balance of payments crisis has been reduced sharply. Significant progress has also been made in stabilizing the financial system and addressing corporate distress, and wide-ranging reforms have made Korea`s economy more open, competitive, and market driven. Notwithstanding these achievements, more needs to be done before the soundness of the corporate and financial sectors is firmly established.
Dust formation and evolution in the ejecta of core-collapse supernovae

Observations of local supernovae over the past couple of decades have reported the presence of dust in the ejecta. The dust masses inferred from observations in mid-infrared and submillimeter wavelengths differ by a factor of 10^2 to 10^4 The composition of dust in the ejecta is yet to be determined with precision. The reddening of the high redshift quasars also indicate the presence of large masses of dust in the early galaxies, the source of which is not yet clear. The sizes of the dust grains in the ejecta control their probability of survival against the reverse-shock(s) in the remnant phase and their contribution to the total dust budget of the galaxy. Core-collapse supernovae and AGB stars are the most important sources of dust in a given galaxy, however their relative contributions are still uncertain. This project aims to quantify the role of core-collapse supernovae as dust producers in the galaxy. I study the production of dust in Type II-P supernova ejecta by coupling the gas-phase chemistry to the dust nucleation and condensation phases using a chemical kinetic approach. Several supernova progenitor masses with homogeneous and clumpy ejecta is assessed to estimate the chemical type and quantity of dust formed. Grain size distributions are derived for all dust components as a function of post-explosion time. The obtained dust properties are used to calculate the spectral energy distributions which are then compared to the estimated fluxes from SN1987A. The chemistry of the gas-phase and the simultaneous formation of dust clusters are described by a chemical network that includes all possible processes efficient at high gas temperatures and densities. The formation of key bimolecular species (e.g., CO, SiO) and dust clusters of silicates, alumina, metal carbides and sulphides, pure metals, and amorphous carbon is considered. The findings suggest the formation of dust in the ejecta with final masses between 0.3-0.14 Mʘ depending on the physical conditions. Silicates, alumina and amorphous carbon stand out as the leading dust components. The grain size distributions are slewed towards large grains, and differ from the usual Mathis, Rumpl & Nordsieck power-law distribution characterising interstellar dust. An increase in the degree of clumpiness and a decrease in the amount of radioactive 56^Ni induce an early formation of dust leading to larger dust mass and bigger grains (~ 0.1-1 μm). These grains are most likely to survive the shock phases and enrich the dust budget of the galaxy. The mass of the progenitor dictates the relative abundances C-rich and O-rich dust components. Our results highlight the fact that dust synthesis in Type II-P supernovae is not a single and simple process, as it is often assumed. They confirm the total dust mass gradually builds up over a time span of ~ 5 years post-outburst, and provide a genuine explanation for the discrepancy between the small amounts of dust formed at early post-explosion times and the large dust masses derived from recent observations of supernova remnants.
Uncovering a tripartite landmark in posterior cingulate cortex

Understanding brain structure-function relationships, and their development and evolution, is central to neuroscience research. Here, we show that morphological differences in posterior cingulate cortex (PCC), a hub of functional brain networks, predict individual differences in macroanatomical, microstructural, and functional features of PCC. Manually labeling 4511 sulci in 572 hemispheres, we found a shallow cortical indentation (termed the inframarginal sulcus; ifrms) within PCC that is absent from neuroanatomical atlases yet colocalized with a focal, functional region of the lateral frontoparietal network implicated in cognitive control. This structural-functional coupling generalized to meta-analyses consisting of hundreds of studies and thousands of participants. Additional morphological analyses showed that unique properties of the ifrms differ across the life span and between hominoid species. These findings support a classic theory that shallow, tertiary sulci serve as landmarks in association cortices. They also beg the question: How many other cortical indentations have we missed?
A CRISPR‐based lateral flow assay for plant genotyping and pathogen diagnostics

Summary Efficient pathogen diagnostics and genotyping methods enable effective disease management and breeding, improve crop productivity and ensure food security. However, current germplasm selection and pathogen detection techniques are laborious, time‐consuming, expensive and not easy to mass‐scale application in the field. Here, we optimized a field‐deployable lateral flow assay, Bio‐SCAN, as a highly sensitive tool to precisely identify elite germplasm and detect mutations, transgenes and phytopathogens in <1 h, starting from sample isolation to result output using lateral flow strips. As a proof of concept, we genotyped various wheat germplasms for the Lr34 and Lr67 alleles conferring broad‐spectrum resistance to stripe rust, confirmed the presence of synthetically produced herbicide‐resistant alleles in the rice genome and screened for the presence of transgenic elements in the genome of transgenic tobacco and rice plants with 100% specificity. We also successfully applied this new assay to the detection of phytopathogens, including viruses and bacterial pathogens in Nicotiana benthamiana, and two destructive fungal pathogens (Puccinia striiformis f. sp. tritici and Magnaporthe oryzae Triticum) in wheat. Our results illustrate the power of Bio‐SCAN in crop breeding, genetic engineering and pathogen diagnostics to enhance food security. The high sensitivity, simplicity, versatility and in‐field deployability make the Bio‐SCAN as an attractive molecular diagnostic tool for diverse applications in agriculture.
Nanoporous Membranes of Densely Packed Carbon Nanotubes Formed by Lipid-Mediated Self-Assembly

Nanofiltration technology faces the competing challenges of achieving high fluid flux through uniformly narrow pores of a mechanically and chemically stable filter. Supported dense-packed 2D-crystals of single-walled carbon nanotube (CNT) porins with ∼1 nm wide pores could, in principle, meet these challenges. However, such CNT membranes cannot currently be synthesized at high pore density. Here, we use computer simulations to explore lipid-mediated self-assembly as a route toward densely packed CNT membranes, motivated by the analogy to membrane-protein 2D crystallization. In large-scale coarse-grained molecular dynamics (MD) simulations, we find that CNTs in lipid membranes readily self-assemble into large clusters. Lipids trapped between the CNTs lubricate CNT repacking upon collisions of diffusing clusters, thereby facilitating the formation of large ordered structures. Cluster diffusion follows the Saffman-Delbrück law and its generalization by Hughes, Pailthorpe, and White. On longer time scales, we expect the formation of close-packed CNT structures by depletion of the intervening shared annular lipid shell, depending on the relative strength of CNT–CNT and CNT–lipid interactions. Our simulations identify CNT length, diameter, and end functionalization as major factors for the self-assembly of CNT membranes.
Second-order optical nonlinear and luminescent properties of Ba2TiSi2O8 nanocrystallized glass

The optical properties of Ba2TiSi2O8 nanocrystals in transparent crystallized glasses were investigated. The transparent nanocrystallized glass with Ba2TiSi2O8 crystals having a particle size of ∼200nm was fabricated by crystallization (at 760 °C for 1 h) of a glass with the stoichiometric composition of Ba2TiSi2O8, i.e., 40BaO∙20TiO2∙40SiO2 glass. Both visible second-harmonic generation (green light, 532 nm) and luminescence (blue light, ∼470nm) could be observed in the transparent Ba2TiSi2O8 nanocrystallized glass, demonstrating the optical multifunctional nanocrystallized material. It was suggested that the blue luminescence from the transparent Ba2TiSi2O8 nanocrystallized glass originated from the oxygen-related defects of the SiO4 unit in the Ba2TiSi2O8 nanocrystals.
Human herpesvirus 6A and 6B and polyomavirus JC and BK infections in renal cell carcinoma and their relationship with p53, p16INK4a, Ki‐67, and nuclear factor‐kappa B expression

There are a limited number of studies regarding the involvement of viruses in the development and pathogenesis of renal cell carcinoma (RCC). In this study, we aimed to discover whether human herpesvirus 6A (HHV‐6A) and 6B (HHV‐6B) and human polyomavirus JC (JCV) and BK (BKV) are associated with RCC and the expression of p53, p16INK4a, Ki‐67, and nuclear factor‐κB (NF‐κB) in patients with RCC. A total of 122 histologically confirmed RCC tissue specimens and 96 specimens of their corresponding peritumoral tissues were included in this prospective study. Nested PCR was performed to amplify viral DNA sequences. Restriction endonuclease analysis was carried out to discriminate between HHV‐6A and HHV‐6B. p53, p16INK4a, Ki‐67, and NF‐κB immunostaining data of the studied tissue specimens were available from our previous study. Statistical analysis was performed to demonstrate the potential associations. HHV‐6B and JCV were detected in 10.7% and 13.9% of patients with RCC, respectively. We did not detect HHV‐6A and BKV in any of RCC tissue specimens. Moreover, no association was found between either of these viruses and RCC. Our study revealed a significant association between HHV‐6B and p53 overexpression. No other associations were found between cellular biomarkers p53, p16INK4a, Ki‐67, and NF‐κB and the studied viruses. The data of this study, though very limited, disprove the involvement of HHV‐6A, HHV‐6B, BKV, and JCV in the initiation or progression of RCC.
Expanding the spectrum of KCNJ6‐related disorders: Milder phenotype with pathological startle responses

Keppen–Lubinsky syndrome is caused by pathogenic variants in KCNJ6, which encodes the inwardly rectifying channel subfamily J6. The four confirmed cases reported to date were characterized by severe intellectual disability, global developmental delay, feeding difficulties, and dysmorphic features. All but one of the cases also had a severe form of lipodystrophy, resulting in tightly adherent facial skin and appearance of premature aging. Here, we describe a 36‐year‐old female with a de novo pathogenic variant in KCNJ6 (NM_002240.5: c.460G>T; p.(Gly154Cys)) presenting with mild intellectual disability, subtle dysmorphic features, obsessive–compulsive disorder, and an exaggerated startle response. This case indicates that KCNJ6‐related disorders should be considered in patients with less pronounced dysmorphic features and milder cognitive impairment, as well as in patients with startle disorders.
Estimation of genetic correlations of two key feed efficiency traits with production traits in male Hu sheep

Abstract Increased body growth and feed efficiency are important for breeding due to expensive feed costs. This study estimated the genetic parameters for two feed efficiency traits [the feed conversion ratio (FCR) and the residual feed intake (RFI)] and other important economic traits in male Hu sheep using 1642 male Hu lambs. The heritability of the RFI was estimated at 0.31 (±0.10)–0.54 (±0.1) and the heritability of the FCR was 0.05 (±0.07)–0.77 (±0.12). There was a negative genetic correlation between rib-eye muscle area traits and RFI. A positive genetic correlation was found between fat deposition traits and feed efficiency traits. The digestive tract weight decreased with the direction of RFI: however, the FCR showed the opposite: A low FCR was accompanied by a high digestive tract weight. The genetic correlation between feed efficiency (RFI and FCR) and rumen weight was negative. Heritability estimates for feed efficiency generate fluctuations with different experimental intervals. The weight of other traits should be reasonably allocated to avoid losses in production and feed efficiency in the selection of feed efficiency traits. The present study added to our understanding of the genetic parameters of sheep under the condition of house feeding.
The druggable transcription factor Fli-1 regulates T cell immunity and tolerance in graft-versus-host disease

Graft-versus-host disease (GVHD), manifesting as either acute (aGVHD) or chronic (cGVHD), presents significant life-threatening complications following allogeneic hematopoietic cell transplantation. Here, we investigated Friend virus leukemia integration 1 (Fli-1) in GVHD pathogenesis and validated Fli-1 as a therapeutic target. Using genetic approaches, we found that Fli-1 dynamically regulated different T cell subsets in allogeneic responses and pathogenicity in the development of aGVHD and cGVHD. Compared with homozygous Fli1-deficient or WT T cells, heterozygous Fli1-deficient T cells induced the mildest GVHD, as evidenced by the lowest Th1 and Th17 cell differentiation. Single-cell RNA-Seq analysis revealed that Fli-1 differentially regulated CD4+ and CD8+ T cell responses. Fli-1 promoted the transcription of Th1/Th17 pathways and T cell receptor–inducible (TCR-inducible) transcription factors in CD4+ T cells, while suppressing activation- and function-related gene pathways in CD8+ T cells. Importantly, a low dose of camptothecin, topotecan, or etoposide acted as a potent Fli-1 inhibitor and significantly attenuated GVHD severity, while preserving the graft-versus-leukemia (GVL) effect. This observation was extended to a xenograft model, in which GVHD was induced by human T cells. In conclusion, we provide evidence that Fli-1 plays a crucial role in alloreactive CD4+ T cell activation and differentiation and that targeting Fli-1 may be an attractive strategy for treating GVHD without compromising the GVL effect.