Miracle-dz/UniFAR-FTUs huggingface dataset:
The loss of dopaminergic neurons in DEC1 deficient mice potentially involves the decrease of PI3K/Akt/GSK3β signaling

Here we study the effects of differentiated embryonic chondrocyte gene 1(DEC1) deficiency on midbrain dopaminergic(DA) neurons in the substantia nigra pars compacta(SNpc) through behavioral, histological and molecular analysis. We have found that compared to the age-matched WT mice, DEC1 deficient mice show a decrease in locomotor activity and motor coordination, which shows the main features of Parkinson’s disease(PD). But there is no significant difference in spatial learning and memory skills between WT and DEC1 KO mice. Compared to the age-matched WT mice, DEC1 deficient mice exhibit the loss of DA neurons in the SNpc and reduction of dopamine and its metabolites in the striatum. The activated caspase-3 and TH/TUNEL+ cells increase in the SNpc of 6- and 12-month-old DEC1 KO mice compared to those of the age-matched WT mice. But we haven't found any NeuN/TUNEL+ cell increase in the hippocampus of the above two types of mice at the age of 6 months. Furthermore, DEC1 deficiency leads to a significant inhibition of PI3K/Akt/GSK3β signaling pathway. Additionally, LiCl could rescue the DA neuron loss of midbrain in the 6-month-old DEC1 KO mice. Taken together, the loss of DA neurons in the DEC1 deficient mice potentially involves the downregulation of PI3K/Akt/GSK3β signaling.
Transhepatic puncture via retrohepatic inferior vena cava:applied anatomical study

Objective: To study the security of transhepatic puncture through retrohepatic inferior vena cava (RIVC),and to provide the anatomical basis on the clinical application of reestablishing the second hepatic hlium (RSHH) and direct the intrahepatic portocaval shunt (DIPS). Methods: Thirty-one normal specimens of livers and RIVC were anatomically observed for understanding the anatomic characteristics of the RIVC and the hepatic vein (HV). Results: (1)length of Retrohepatic IVC: (7.01±1.30)cm; Safe area of the transhepatic puncture for the RIVC: (5.43±1.23) cm,95% confidence interval (CL): 3.02-7.84 cm. 2. Hepatic vein: Upper group: diameters of the RHV,MHV and LHV are (5.3±3.6) mm,(8.7±1.9) mm and (9.3±1.8) mm respectively. LHV and MHV have the same port in 28 specimens (90.3%). The three HVs has the independent port in 28 specimens (9.7%); Lower group: for the different diameters of the small HVs (greater than 10mm,diameters in 10-5mm,and smaller than 5mm),the percentage of appearance of the specimens was 35.5%,87.1% and 96.8% respectively; constituent ratio of the small HV was 5.0%,71.0%,24.0% respectively; distributing in right region of the lower RIVC,anterior and right region of the lower RIVC,and anterior and left region of the lower RIVC; (3)Transhepatic puncture distance of the routine TIPS and DIPS: TIPS via the RHV was (38.6±8.1) mm; TIPS via the MHV was (46.6±8.2) mm; and DIPS was (31.2±7.9) mm. The difference among the three groups were significant (P0.001). The distance of the transhepatic puncture of DIPS was shortest,and that of TIPS via the MHV was longest. Conclusions: (1)(54.3±12.3) mm on RIVC are safe for the transhepatic puncture. (2) There are small HVs of different diameters on the lower part of RIVC. The samller the diameter is,the higher the appearance percentage is,and the more of the small HVs are. (3)The distance of the transhepatic puncture of DIPS is shortest,and the TIPS via the MHV is longest.
Spatial dynamics of the insulin receptor in living neurons

Insulin signaling through the insulin receptor has long been studied in classic target organs, such as adipose tissue and skeletal muscle, where one of its effects is to increase glucose uptake. Insulin and insulin receptor are present in many areas of the brain, but the functions of brain insulin signaling outside feeding circuits are not well defined. It has been proposed that hippocampal insulin signaling is important for memory, that brain insulin signaling is deficient in Alzheimer's disease, and that intranasal insulin treatment improves cognition, but the mechanisms remain unclear and do not seem to involve increased glucose uptake by neurons. The molecular behavior of the insulin receptor itself is not well known in living neurons; therefore, we investigated the spatial dynamics of the insulin receptor on somatodendritic membranes of live rat hippocampal neurons in culture. Using single‐molecule tracking of quantum dot‐tagged insulin receptors and single‐particle tracking photoactivation localization microscopy, we show that the insulin receptor is distributed over both dendritic shafts and spines. Using colocalization with synaptic markers, we also show that in contrast to the glutamate receptor subunit glutamate receptor subunit A1, the dynamics of the insulin receptor are not affected by association with excitatory synapses; however, the insulin receptor is immobilized by components of inhibitory synapses. The mobility of the insulin receptor is reduced both by low concentrations of the pro‐inflammatory cytokine tumor necrosis factor α and by cholesterol depletion, suggesting an association with sphingolipid‐rich membrane domains. On the other hand, the insulin receptor dynamics in hippocampal neurons are not affected by increased excitatory signaling. Finally, using real‐time single‐event quantification, we find evidence of strong insulin receptor exocytosis on dendritic shafts. Our results suggest an association of the neuronal insulin receptor with specific elements of the dendritic shaft, rather than excitatory synapses.
Characterization of an Electronic Corneal Prosthesis System

ABSTRACT Purpose Corneal opacity is a leading cause of reversible blindness worldwide. An electronic corneal prosthesis, or intraocular projector, could potentially restore high-quality vision without need for corneal clarity. Materials and Methods Four intraocular projection systems were constructed from commercially available electronic components and encased in biocompatible plastic housing. They were tested for optical properties, biocompatibility, heat dissipation, waterproofing, and accelerated wear. A surgical implantation technique was developed. Results Intraocular projectors were produced of a size that can fit within the eye. Their optics produce better than 20/200 equivalent visual acuity. MTT assay demonstrated no cytotoxicity of devices in vitro. Temperature testing demonstrated less than 2°C increase in temperature after 1 h. Three devices lasted over 12 weeks under accelerated wear conditions. Implantation surgery was demonstrated via corneal trephination insertion in a cadaver eye. Conclusion This is the first study to demonstrate and characterize fully functional intraocular projection systems. This technology has the potential to be an important new tool in the treatment of intractable corneal blindness.
Levels of Retinal Amyloid-β Correlate with Levels of Retinal IAPP and Hippocampal Amyloid-β in Neuropathologically Evaluated Individuals

Background: Previous studies have used immunohistology to demonstrate Alzheimer’s disease (AD) characteristic accumulation of amyloid-β (Aβ) in the retina of AD patients, a finding indicating retina examination as a potential diagnostic tool for AD pathology. Objective: To further explore this idea by investigating whether levels of Aβ42 and Aβ40 in retina are associated with corresponding levels in hippocampus, neuropathological assessments, apolipoprotein E (APOE) genotype, and levels of islet amyloid polypeptide (IAPP). Methods: Levels of high molecular weight (HMW) Aβ42, Aβ40, and IAPP in ultra-centrifuged homogenates of retina and hippocampus from patients with AD, multiple sclerosis, AD with Lewy bodies, and non-demented controls were analyzed using Mesoscale Discovery electrochemiluminescence technology employing immunoassay and enzyme-linked immunosorbent assay. Results: Higher levels of retinal and hippocampal Aβ42-HMW, Aβ40-HMW, and IAPP-HMW were found in individuals with high neuropathological scores of Aβ plaques and in individuals carrying the APOE ɛ4 allele. The retinal levels of Aβ42-HMW and Aβ40-HMW correlated with corresponding levels in hippocampus as well as with neurofibrillary tangles (NFT) and Aβ scores. Retinal IAPP-HMW correlated with retinal levels of Aβ42-HMW and with NFT and Aβ scores. Conclusion: These results show that different isoforms of Aβ can be detected in the human retina and moreover support the growing number of studies indicating that AD-related pathological changes occurring in the brain could be reflected in the retina.
An Overview of Expanded Newborn Screening for Inborn Errors of Metabolism

INTRODUCTION Newborn screening for metabolic disorders has been in place since the early 1960’s when screening began for PKU using the “Guthrie test,” developed by Robert Guthrie (1). Congenital hypothyroidism, galactosemia, and sickling hemoglobinopathies were later added to many newborn-screening programs. Although the same blood spot mechanism for collecting samples is used, the development of tandem mass spectrometry (MS/MS) allows us to identify abnormal analytes associated with a variety of disorders of amino acid, organic acid and fat metabolism. Often mistakenly referred to as the “PKU test,” newborn screening has advanced such that knowledge of the scope of testing, as well as the recommended confirmatory follow-up is helpful in order for the primary care physician to provide the first line of communication to families who are identified with an abnormal result. This article provides an overview of expanded newborn screening procedures and follow-up, focusNUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #41
Mannose binding lectin polymorphisms in systemic lupus erythematosus in Spain

Low mannose binding lectin (MBL) producer genotypes have been considered as a systemic lupus erythematosus (SLE) risk factor. The aim of this study was to explore whether polymorphisms in the MBL gene are associated with susceptibility to SLE and disease-specific clinical manifestations or with disease severity in SLE patients in Son Llàtzer Hospital. MBL2 exon 1 and promoter polymorphisms were genotyped and MBL plasma levels were quantified by ELISA in 39 SLE cases and in 96 healthy controls. High MBL producer genotypes HYPA and LXPA were the most frequent haplotypes (65 and 62 participants, respectively). LYQC/HYPD, LXPA/LYQC and LYPB/HYPD were only found in SLE, and all of them were related to severe MBL deficiency. SLE patients showed a trend towards more severe MBL deficiency (MBL <100 ng/mL) compared to controls (10 [25.6%] and 11 [11.46%] respectively, P = 0.07). The wild-type genotype was more frequent in controls compared to SLE. The trend towards more severe MBL deficiency in SLE and the fact that some of the low-MBL producer genotypes were only found in SLE patients, suggest that low MBL levels or MBL2 variant could be a risk factor for the development of SLE.
Toxicological study of metal and metal oxide nanoparticles in zebrafish

Metal and metal oxide nanoparticles have been widely used in catalytic, electronic and biomedical fields. It is necessary to investigate their toxicity and potential hazards to human and aquatic ecosystems. Zebrafish (Danio rerio), as a promising animal model, has been increasingly utilized to assess the toxicity of nanoparticles. Zebrafish has numerous characteristics for toxicity evaluation, such as short life cycle and high fecundity. This review describes the advantages of using zebrafish in the toxicity assessment of metal and metal oxide nanoparticles. Then we focus on the toxic effects, particularly the acute toxicity and the chronic ones, induced by nanoparticles in zebrafish. Target organ toxicities are also mentioned, including immunotoxicity, developmental toxicity, neurotoxicity, reproductive toxicity, cardiovascular toxicity and hepatotoxicity. The toxic effects of selected metal nanoparticles, including Au, Ag, Cu, and metal oxide nanoparticles such as TiO2, Al2O3, CuO, NiO and ZnO, as well as the underlying mechanisms of nanoparticles causing these effects, are also highlighted and described in detail. Furthermore, we introduce the general factors that affect nanoparticle‐induced toxicity in zebrafish. The drawbacks and advantages of using the zebrafish model in nanotoxicity studies are also argued. Finally, we suggest that the application of zebrafish to assess chronic toxicity of metal and metal oxide nanoparticles and the joint toxicity of metal and metal oxide nanoparticles and other pollutants could be hot topics in nanotoxicology.
Predicting the Number of Fibular Segments to Reconstruct Mandibular Defects

Several classification schemes have been proposed to categorize mandibular defects following surgical resection; however, there is a paucity of data to guide an optimal reconstruction. This study examines the feasibility of using a geometric algorithm to simplify and determine the optimal reconstruction for a given mandibular defect. This algorithm is then applied to three different mandible defect classification schemes to correlate the defect type and number of bony segments required for reconstruction.
Protein Corona-triggered Catalytic Inhibition of Insufficient POSS Polymer-caged Gold Nanoparticles for Sensitive Colorimetric Detection of Metallothioneins.

Metallothioneins (MTs) are important biomarkers for the early diagnosis of heavy metal poisoning and malignancies. Convenient and cost-effective approaches for the rapid detection of MTs are therefore highly desirable for clinical monitoring. Herein, by taking advantage of the enzyme-mimetic activity of nanoparticles and protein corona-based recognition, insufficient polyhedral oligomeric silsesquioxane (POSS) polymer-caged gold nanoparticles (denoted as PP-AuNPs) are developed for the sensitive colorimetric analysis of MTs. In the presence of MTs, the catalytic reduction of yellow 4-nitrophenol to colorless 4-aminophenol is inhibited due to masking of the exposed PP-AuNPs catalytic surface with MTs corona. MTs are quantified by the presented color contrast with a superior sensitivity up to a 1.5 nM detection limit. Most importantly, the heavy metal ion- and aptamer-free PP-AuNPs platform exhibits excellent selectivity towards MTs over various ions, neutral biomolecules and protein species, and successful applications are demonstrated by the detection of MTs in complex biological samples.
Hierarchical Hybrid Enrichment: Multitiered Genomic Data Collection Across Evolutionary Scales, With Application to Chorus Frogs (Pseudacris)

Abstract Determining the optimal targets of genomic subsampling for phylogenomics, phylogeography, and population genomics remains a challenge for evolutionary biologists. Of the available methods for subsampling the genome, hybrid enrichment (sequence capture) has become one of the primary means of data collection for systematics, due to the flexibility and cost efficiency of this approach. Despite the utility of this method, information is lacking as to what genomic targets are most appropriate for addressing questions at different evolutionary scales. In this study, first, we compare the benefits of target loci developed for deep- and shallow scales by comparing these loci at each of three taxonomic levels: within a genus (phylogenetics), within a species (phylogeography), and within a hybrid zone (population genomics). Specifically, we target evolutionarily conserved loci that are appropriate for deeper phylogenetic scales and more rapidly evolving loci that are informative for phylogeographic and population genomic scales. Second, we assess the efficacy of targeting multiple-locus sets for different taxonomic levels in the same hybrid enrichment reaction, an approach we term hierarchical hybrid enrichment. Third, we apply this approach to the North American chorus frog genus Pseudacris to answer key evolutionary questions across taxonomic and temporal scales. We demonstrate that in this system the type of genomic target that produces the most resolved gene trees differs depending on the taxonomic level, although the potential for error is substantially lower for the deep-scale loci at all levels. We successfully recover data for the two different locus sets with high efficiency. Using hierarchical data targeting deep and shallow levels: we 1) resolve the phylogeny of the genus Pseudacris and introduce a novel visual and hypothesis testing method that uses nodal heat maps to examine the robustness of branch support values to the removal of sites and loci; 2) estimate the phylogeographic history of Pseudacris feriarum, which reveals up to five independent invasions leading to sympatry with congener Pseudacris nigrita to form replicated reinforcement contact zones with ongoing gene flow into sympatry; and 3) quantify with high confidence the frequency of hybridization in one of these zones between P. feriarum and P. nigrita, which is lower than microsatellite-based estimates. We find that the hierarchical hybrid enrichment approach offers an efficient, multitiered data collection method for simultaneously addressing questions spanning multiple evolutionary scales. [Anchored hybrid enrichment; heat map; hybridization; phylogenetics; phylogeography; population genomics; reinforcement; reproductive character displacement. ]
Glide Mirror Plane Protected Nodal-Loop in Anisotropic Half-Metallic MnNF Monolayer.

Two-dimensional (2D) nodal-loop (NL) semimetals have attracted tremendous attentions for their abundant physics and potential device applications, whereas the realization of gapless NL semimetals robust against spin-orbit coupling (SOC) remains a big challenge. Recently, breakthroughs have been made with the realization of gapless NL semimetals in 2D half-metallic materials, where NLs were protected by a horizontal mirror plane symmetry. Here we first propose an alternative nonsymmorphic horizontal glide mirror plane symmetry which could protect the NLs in 2D materials. Based on comprehensive first-principles calculations and symmetry analysis, we found that the glide mirror symmetry together with intrinsic out-of-plane spin polarization can protect the NL against SOC in a half-metallic semimetal namely MnNF monolayer. Moreover, we predict that the MnNF monolayer has strong anisotropic characteristics, tunable band structure by changing the magnetization direction and 100% spin-polarized transport properties. Our work not only provides a novel 2D half-metallic semimetal with strong anisotropy, but also broadens the scope of 2D nodal-loop materials.
The challenge of using routinely collected data to compare hospital admission rates by ethnic group: a demonstration project in Scotland.

BACKGROUND Recording patients' ethnic group supports efforts to achieve equity in health care provision. Before the Equality Act (2010), recording ethnic group at hospital admission was poor in Scotland but has improved subsequently. We describe the first analysis of the utility of such data nationally for monitoring ethnic variation. METHODS We analysed all in-patient or day case hospital admissions in 2013. We imputed missing data using the most recent ethnic group recorded for a patient from 2009 to 2015. For episodes lacking an ethnic code, we attributed known ethnic codes proportionately. Using the 2011 Census population, we calculated rates and rate ratios for all-cause admissions and ischaemic heart diseases (IHDs) directly standardized for age. RESULTS Imputation reduced missing ethnic group codes from 24 to 15% and proportionate redistribution to zero. While some rates for both all-cause and IHD admissions appeared plausible, unexpectedly low or high rates were observed for several ethnic groups particularly amongst White groups and newly coded groups. CONCLUSIONS Completeness of ethnicity recoding on hospital admission records has improved markedly since 2010. However the validity of admission rates based on these data is variable across ethnic groups and further improvements are required to support monitoring of inequality.
Biotechnology and Bioengineering

Funding information Singapore Institute of Manufacturing Technology, Grant/Award Number: A*STAR JCO Grant 15302FG152 Abstract Disruption of the blood–brain barrier (BBB) leads to various neurovascular diseases. Development of therapeutics required to cross the BBB is difficult due to a lack of relevant in vitro models. We have developed a three‐dimensional (3D) microfluidic BBB chip (BBBC) to study cell interactions in the brain microvasculature and to test drug candidates of neurovascular diseases. We isolated primary brain microvascular endothelial cells (ECs), pericytes, and astrocytes from neonatal rats and cocultured them in the BBBC. To mimic the 3D in vivo BBB structure, we used type I collagen hydrogel to pattern the microchannel via viscous finger patterning technique to create a matrix. ECs, astrocytes, and pericytes were cocultured in the collagen matrix. The fluid flow in the BBBC was controlled by a pump‐free strategy utilizing gravity as driving force and resistance in a paper‐based flow resistor. The primary cells cultured in the BBBC expressed high levels of junction proteins and formed a tight endothelial barrier layer. Addition of tumor necrosis factor alpha to recapitulate neuroinflammatory conditions compromised the BBB functionality. To mitigate the neuroinflammatory stimulus, we treated the BBB model with the glucocorticoid drug dexamethasone, and observed protection of the BBB. This BBBC represents a new simple, cost‐effective, and scalable in vitro platform for validating therapeutic drugs targeting neuroinflammatory conditions.
Short‐ and long‐term reproducibility of BOLD signal change induced by breath‐holding at 1.5 and 3 T

Cerebrovascular reactivity (CVR) can give insight into the cerebrovascular function. CVR can be estimated by measuring a blood‐oxygen‐level‐dependent (BOLD) response combined with breath‐holding (BH). The reproducibility of this technique has been addressed and existing studies have focused on short‐term reproducibility using a 3 T magnetic resonance imaging (MRI) system. However, little is known about the long‐term reproducibility of this procedure and the corresponding reproducibility using a 1.5 T MRI system. Here, we systematically examined the short‐ and long‐term reproducibility of BOLD responses to BH across field strengths. Nine subjects participated in three MRI sessions separated by 30 minutes (sessions 1 and 2: short term) and 68–92 days (sessions 1 and 3, long term) at both 1.5 and 3 T MRI. Our findings revealed that significant differences between field strengths were detected in the activated gray matter volume and BOLD signal change (both P < 0.001), with smaller magnitudes at 1.5 T. However, activation patterns were reproducible, independent of the time interval, brain region or field strength. All interscan coefficient of variation values were below the 33% fiducial limit, and the intraclass correlation coefficient values were above 0.4, which is usually considered the acceptability limit in functional studies. These findings suggest that the response of BOLD signal to BH for assessing CVR is reproducible over time at 1.5 and 3 T. This technique can be considered a tool for monitoring longitudinal changes in patients with cerebrovascular diseases, and its use should be encouraged for clinical 1.5 T MRI systems.