Miracle-dz/UniFAR-FTUs huggingface dataset:
Celsr family genes are dynamically expressed in embryonic and juvenile zebrafish

The Cadherin EGF LAG seven‐pass G‐type receptor (Celsr) family belongs to the adhesion G‐protein coupled receptor superfamily. In most vertebrates, the Celsr family has three members (CELSR1–3), whereas zebrafish display four paralogues (celsr1a, 1b, 2, 3). Although studies have shown the importance of the Celsr family in planar cell polarity, axonal guidance, and dendritic growth, the molecular mechanisms of the Celsr family regulating these cellular processes in vertebrates remain elusive. Zebrafish is an experimentally more amenable model to study vertebrate development, as zebrafish embryos develop externally, optically transparent, remain alive with malformed organs, and zebrafish is genetically similar to humans. Understanding the detailed expression pattern is the first step of exploring the functional mechanisms of the genes involved in development. Thus, we report the spatiotemporal expression pattern of Celsr family members in zebrafish nervous tissues. Our analysis shows that celsr1b and celsr2 are expressed maternally. In embryos, celsr1a, celsr1b, and celsr2 are expressed in the neural progenitors, and celsr3 is expressed in all five primary neural clusters of the brain and mantle layer of the spinal cord. In juvenile zebrafish, celsr1a, celsr1b, and celsr2 are presumably expressed in the neural progenitor enriched regions of the CNS. Therefore, the expression pattern of zebrafish Celsr family members is reminiscent of patterns described in other vertebrates or mammalian speciate. This indicates the conserved role of Celsr family genes in nervous system development and suggests zebrafish as an excellent model to explore the cellular and molecular mechanisms of Celsr family genes in vertebrate neurogenesis.
Comparative evaluation on the toxic effect of silver (Ag) and zinc oxide (ZnO) nanoparticles on different trophic levels in aquatic ecosystems: A review

Silver (Ag) and zinc oxide (ZnO) are considered to be harmful nanoparticles (NPs) to the aquatic organisms as their intake causes toxic impacts to wildlife, through direct ingestion or by the transference along trophic levels. Over usage and ultimate disposal of metallic particles from the industries subsequently lead to pollution of the aquatic environment. Exposure of NPs in aquatic ecosystem alters biological and physicochemical parameters of the water and aquatic organisms and determines their potential ecotoxicological impacts. Prolonged exposure of aquatic organisms to these NPs results in differential bioaccumulation and distribution into internal organs like liver, kidney, gills, brain, and muscle tissue. The contact of NPs to aquatic organisms induces various types of toxic traits including cytotoxicity, genotoxicity, and epigeneticity. Taking this in consideration, this present review focuses on the comparative toxic impact of ZnO and Ag NPs towards both vertebrates and invertebrates in aquatic ecosystems.
A Combined Ultrafiltration/Diafiltration Process for the Purification of Oncolytic Measles Virus

Measles virus (MV) is an important representative of a new class of cancer therapeutics known as oncolytic viruses. However, process intensification for the downstream purification of this fragile product is challenging. We previously found that a mid-range molecular weight cut-off (300 kDa) is optimal for the concentration of MV. Here, we tested continuous and discontinuous diafiltration for the purification of MV prepared in two different media to determine the influence of high and low protein loads. We found that a concentration step before diafiltration improved process economy and MV yield when using either serum-containing or serum-free medium. We also found that discontinuous diafiltration conferred a slight benefit in terms of the permeate flow, reflecting the repetitive dilution steps and the ability to break down parts of the fouling layer on the membrane. In summary, the combined ultrafiltration/diafiltration process is suitable for the purification of MV, resulting in the recovery of ~50% infectious virus particles with a total concentration factor of 8 when using 5 diavolumes of buffer.
Altered functional connectivity during hypoglycaemia in type 1 diabetes

Behavioural responses to hypoglycaemia require coordinated recruitment of broadly distributed networks of interacting brain regions. We investigated hypoglycaemia-related changes in brain connectivity in people without diabetes (ND) and with type 1 diabetes with normal (NAH) or impaired (IAH) hypoglycaemia awareness. Two-step hyperinsulinaemic hypoglycaemic clamps were performed in 14 ND, 15 NAH and 22 IAH participants. BOLD timeseries were acquired at euglycaemia (5.0 mmol/L) and hypoglycaemia (2.6 mmol/L), with symptom and counter-regulatory hormone measurements. We investigated hypoglycaemia-related connectivity changes using established seed regions for the default mode (DMN), salience (SN) and central executive (CEN) networks and regions whose activity is modulated by hypoglycaemia: the thalamus and right inferior frontal gyrus (RIFG). Hypoglycaemia-induced changes in the DMN, SN and CEN were evident in NAH (all p < 0.05), with no changes in ND or IAH. However, in IAH there was a reduction in connectivity between regions within the RIFG (p = 0.001), not evident in the ND or NAH groups. We conclude that hypoglycaemia induces coordinated recruitment of the DMN and SN in diabetes with preserved hypoglycaemia awareness which is absent in IAH and ND. Changes in connectivity in the RIFG, a region associated with attentional modulation, may be key in impaired hypoglycaemia awareness.
Application of RBI Technology in Atmospheric Storage Tanks

According to API 581 and principle of risk based inspection(RBI) on atmospheric storage tanks(AST),risk evaluation was made on 20 storage tanks by using AST RBI software of DNV.Results show that there is no high risk item,and the percentage of medium high risk,medium risk and low risk are respectively 12.5%,67.5% and 20%. The inspection measure and strategy for risk reduction were made according to different risk level of the storage tanks.Moreover,a medium high risk tank and a medium risk tank were picked out and taken floor magnetic flux leakage(MFL) testing.The reliability of RBI has been confirmed by the compare of MFL testing and evaluation results.
Plasma Cell-Free DNA Integrity Assessed by Automated Electrophoresis Predicts the Achievement of Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer

PURPOSE The study of plasma cell-free DNA integrity (cfDI) has shown potential for providing useful information in neoplastic patients. The aim of this study is to estimate the accuracy of an electrophoresis-based method for cfDI evaluation in the assessment of pathologic complete response (pCR) in patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT). PATIENTS AND METHODS Fifty-one patients with BC undergoing anthracycline-/taxane-based NACT were recruited. Plasma samples were collected from each patient at diagnosis (t0), after anthracycline administration (t1), and after NACT completion (t2). The concentration of differently sized cell-free DNA fragments was assessed by automated electrophoresis. cfDI, expressed as cfDI index, was calculated as the ratio of 321-1,000 bp sized fragment concentration to 150-220 bp sized fragment concentration assessed at t2. cfDI index was then used to build an exploratory classifier for BC response to NACT, directly comparing its sensitivity and specificity with magnetic resonance imaging (MRI), through bootstrapped logistic regression. RESULTS cfDI index was assessed on 38 plasma samples collected from as many patients at t2, maintaining a 30/70 ratio between pCR and non-pCR patients. cfDI index showed an area under the receiver operating characteristic curve in predicting the achievement of pCR of 81.6, with a cutoff above 2.71 showing sensitivity = 81.8 and specificity = 81.5. The combination of cfDI index and MRI showed, in case of concordance, an area under the receiver operating characteristic curve of 92.6 with a predictive value of complete response of 87.5 and a predictive value of absence of complete response of 94.7. CONCLUSION cfDI index measured after NACT completion shows great potential in the assessment of pCR in patients with BC. The evaluation of its use in combination with MRI is strongly warranted in prospective studies. Plasma DNA fragmentation assessment predicts response to neoadjuvant chemotherapy in breast cancer.
NMR Detection and Structural Modeling of the Ethylene Receptor LeETR2 from Tomato

The gaseous plant hormone ethylene influences many physiological processes in plant growth and development. Plant ethylene responses are mediated by a family of ethylene receptors, in which the N-terminal transmembrane domains are responsible for ethylene binding and membrane localization. Until now, little structural information was available on the molecular mechanism of ethylene responses by the transmembrane binding domain of ethylene receptors. Here, we screened different constructs, fusion tags, detergents, and purification methods of the transmembrane sensor domain of ethylene receptors. However, due to their highly hydrophobic transmembrane domain (TMD), only a KSI-fused LeETR21–131 from tomato yielded a good-quality nuclear magnetic resonance (NMR) spectrum in the organic solvent. Interestingly, a dimer model of LeETR21–131 built by the AlphaFold2 algorithm showed greatly converged structures. The interaction analysis of ethylene and LeETR21–131 using molecular docking and molecular dynamics (MD) simulations demonstrated the potential binding sites of ethylene in LeETR21–131. Our exploration provides valuable knowledge for further understanding of the ethylene-perception process in ethylene receptors.
FXS causing missense mutations disrupt FMRP granule formation, dynamics, and function

Fragile X Syndrome (FXS) is the most prevalent cause of inherited mental deficiency and is the most common monogenetic cause of autism spectral disorder (ASD). Here, we demonstrate that disease-causing missense mutations in the conserved K homology (KH) RNA binding domains (RBDs) of FMRP cause defects in its ability to form RNA transport granules in neurons. Using molecular, genetic, and imaging approaches in the Drosophila FXS model system, we show that the KH1 and KH2 domains of FMRP regulate distinct aspects of neuronal FMRP granule formation, dynamics, and transport. Furthermore, mutations in the KH domains disrupt translational repression in cells and the localization of known FMRP target mRNAs in neurons. These results suggest that the KH domains play an essential role in neuronal FMRP granule formation and function which may be linked to the molecular pathogenesis of FXS.
Discriminating predation attempt outcomes during natural foraging using the post-buzz pause in the Japanese large-footed bat, Myotis macrodactylus

Bats emit a series of echolocation calls with an increasing repetition rate (the terminal buzz), when attempting to capture prey. This is often used as an acoustic indicator of prey-capture attempts. However, because it is directly linked to foraging efficiency, predation success is a more useful measure than predation attempts in ecological research. The characteristics of echolocation calls that consistently signify predation success across different situations have not been identified. Due to additional influencing factors, identification of these characteristics is particularly challenging for wild bats foraging in their natural environment compared to those in flight chambers. This study documented the natural foraging behavior of wild Japanese large-footed bat Myotis macrodactylus using synchronized acoustic and video recordings. From the video recordings, we could assign 137 attacks to three outcome categories: prey captured (51.8%), prey dropped (29.2%), and failed attempt (19%). Based on previous indications from laboratory studies that the length of the silent interval following the terminal buzz (post-buzz pause) might reflect the prey capture outcome, we compared post-buzz pause durations among categories of attack outcomes. The post-buzz pause was longest in the case of successful capture, suggesting that the length of the post-buzz pause is a useful acoustic indicator of predation success during natural foraging in M. macrodactylus. Our finding will advance the study of bat foraging behavior using acoustic data, including estimations of foraging efficiency and analyses of feeding habitat quality. Summary statement We investigated the natural foraging behavior of wild Myotis macrodactylus and found that the length of the post-buzz pause is a useful acoustic indicator of predation success.
Gray matter volumetric correlates of dimensional impulsivity traits in children: Sex differences and heritability

Previous research investigated the cerebral volumetric correlates of impulsivity largely in moderate‐sized samples and few have examined the distinct correlates of dimensions of impulsivity, sex differences, or heritability of the correlates. Here, we performed voxel‐based morphometry analysis of data (n = 11,474; 5,452 girls, 9–10 years) curated from the Adolescent Brain Cognition Development project. In a linear regression with all five UPPS‐P subscores as regressors and age in months, total intracranial volume, study site, and scanner model as covariates, higher levels of lack of premeditation, and sensation seeking were correlated with larger cortical and subcortical gray matter volumes (GMVs). In contrast, higher positive urgency was correlated with smaller GMVs in many of the same regions. The dimensional impulsivity traits also involved distinct volumetric correlates, with, for instance, sensation seeking and positive urgency specifically implicating bilateral caudate head/mid‐cingulate cortex and bilateral lateral orbitofrontal cortex/left precentral gyrus, respectively. Boys relative to girls scored higher in all impulsivity dimensions. Girls relative to boys showed significantly stronger positive and negative correlations between sensation seeking and insula, putamen, and inferior frontal gyrus (IFG) GMVs and between positive urgency and cingulate cortex, insula, and IFG GMVs, respectively. With a subsample of twins, the dimensional impulsivity traits were weakly to moderately heritable in both girls and boys, and the GMV correlates were highly heritable in girls and boys combined. These findings collectively suggest shared and nonshared as well as sex differences in the cerebral volumetric bases of dimensional impulsivity traits and may facilitate research of externalizing psychopathology in children.
Oxygen Self-Supply Engineering-Ferritin for the Relief of Hypoxia in Tumors and the Enhancement of Photodynamic Therapy Efficacy.

Hypoxia is a hallmark of the tumor microenvironment (TME) that promotes tumor development and metastasis. Photodynamic therapy (PDT) is a promising strategy in the treatment of tumors, but it is limited by the lack of oxygen in TME. In this work, an O2 self-supply PDT system is constructed by co-encapsulation of chlorin e6 (Ce6) and a MnO2 core in an engineered ferritin (Ftn), generating a nanozyme promoted PDT nanoformula (Ce6/Ftn@MnO2 ) for tumor therapy. Ce6/Ftn@MnO2 exhibits a uniform small size (15.5 nm) and high stability due to the inherent structure of Ftn. The fluorescence imaging and immunofluorescence analysis demonstrate the pronounced accumulation of Ce6/Ftn@MnO2 in the tumors of mice, and the treatment significantly decreases the expression of hypoxia-inducible factor (HIF)-1α. The Ce6/Ftn@MnO2 nanoplatform exerts a more potent anti-tumor efficacy with negligible damage to normal tissues compared to the treatment with free Ce6. Moreover, the weak acidity and the presence of H2 O2 in TME significantly enhances the r1 relativity of Ce6/Ftn@MnO2 , resulting in a prominent enhancement of MRI imaging in the tumor. This bio-mimic Ftn strategy not only improves the in vivo distribution and retention of Ce6, but also enhances the effectiveness and precision of PDT by TME modulation.
Error inconsistency does not generally inhibit saccadic adaptation: Support for linear models of multi‐gainfield adaptation

This study examined saccade adaptation induced by intrasaccadic target steps (ITS). By manipulating the ITS, we investigated potential effects of the consistency of the feedback error on saccade adaptation, which would provide evidence against the linearity of standard models of visuomotor adaptation. Previous studies addressing saccade adaptation arrived at different interpretations, but in these experiments only a single saccade amplitude was trained rather than a variety of saccade amplitudes in random order (mixed training). We extend previous studies by testing for effects of error consistency under additional control conditions described by the factors training protocol (single‐amplitude/mixed), ITS direction (onward/backward), and adaptation phase (training/washout). Adaptation dynamics were assessed using a model of “multi‐gainfield adaptation” developed by tailoring an existing linear model for visuomotor adaptation of movements with multiple target positions to gain adaptation of saccades with multiple amplitudes. The total adaptive change did not depend on the consistency of the ITS in either mixed or single‐amplitude training. The initial adaptation speed was lower with inconsistent ITS. However, the effect on adaptation speed occurred only during amplitude reduction and not during enlargement or washout. These results corroborate the linearity of saccade adaptation in that the mean error is the main factor determining the total adaptive change, independent of error consistency. The multi‐gainfield adaptation model was confirmed in that the retention rate and error sensitivity did not depend on the training protocol. The absence of effects of error consistency on saccade adaptation is relevant in the context of adaptive deficits in movement disorders.
Vault RNA1–1 riboregulates the autophagic function of p62 by binding to lysine 7 and arginine 21, both of which are critical for p62 oligomerization

Cellular processes can be regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational mechanisms. We have recently shown that the small, noncoding vault RNA1–1 negatively riboregulates p62 oligomerization in selective autophagy through direct interaction with the autophagic receptor. This function is highly specific for this Pol III transcript, but the determinants of this specificity and a mechanistic explanation of how vault RNA1–1 inhibits p62 oligomerization are lacking. Here, we combine biochemical and functional experiments to answer these questions. We show that the PB1 domain and adjacent linker region of p62 (aa 1–122) are necessary and sufficient for specific vault RNA1–1 binding, and we identify lysine 7 and arginine 21 as key hinges for p62 riboregulation. Chemical structure probing of vault RNA1–1 further reveals a central flexible loop within vault RNA1–1 that is required for the specific interaction with p62. Overall, our data provide molecular insight into how a small RNA riboregulates protein–protein interactions critical to the activation of specific autophagy.
Expanded carrier screening in the United States: A systematic evidence review exploring client and provider experiences

The aim of carrier screening is to identify prospective parents at risk of having a pregnancy affected with an autosomal recessive or X‐linked disorder. Though minimal guideline‐based screening is available, expanded carrier screening (ECS) is quickly becoming a feasible option for the general population due to its growing availability and affordability. However, the impact of ECS on clients and providers remains relatively unexplored. We performed a systematic evidence review to identify publications describing client‐, provider‐, and test‐related outcomes. We searched several biomedical databases for articles published between January 1, 2003 and May 31, 2021. Studies were eligible for inclusion if they described genetic counseling and/or genetic testing for carrier screening (minimal guideline‐based or ECS) in a prenatal or preconception setting in the United States. Title and abstract screening were performed using the Raayan web application or customized Google Forms. Full‐text review and data extraction of included articles were performed using custom Google Forms. Two researchers performed a multistep selection process independently for validation purposes. Of 5413 unique articles screened, 36 studies were included with several studies contributing to multiple outcomes. Twenty described outcomes relating to patients/clients, 10 described provider‐based outcomes, and 16 described test‐based outcomes. Findings suggest that client and provider perceptions of ECS and minimal guideline‐based carrier screening are multifaceted. Though clients have expressed desire for ECS, clinical uptake and impact on reproductive decision‐making varies. Additionally, though genetic counselors seem to be comfortable with ECS, most other reproductive care providers seem to prefer minimal guideline or ancestry‐based screening due to perceived barriers, such as time needed for ECS results disclosure and follow‐up, as well as the desire to have panels set by professional societies/recommendations. There are limitations within the gathered literature, leading to potential uncertainty in the generalizability of our review. We outline several recommendations for future studies, including the need to examine variant interpretation and use of next‐generation sequencing.
Self-Rated Benefits of Auditory Performance after Bonebridge Implantation in Patients with Conductive or Mixed Hearing Loss, or Single-Sided Deafness

The Bonebridge implant can be a satisfactory solution for patients with conductive or mixed hearing loss (CHL or MHL), or with single-sided deafness (SSD). The aim of the study was to assess patients’ self-reported benefits with the Bonebridge and characterize the relationships between pre-implantation audiometric data, auditory functioning, and satisfaction after implantation. A focus was to see whether different types of hearing loss were associated with particular benefits. The study sample consisted of 81 patients. Procedures comprised pure tone audiometry before implantation, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, and a structured interview asking about satisfaction. Statistically significant improvements after implantation were found in all groups (CHL, MHL, SSD) on the APHAB questionnaire. In the structured interview, patients with SSD were the least satisfied. No significant correlation was found between pre-operative air-bone gap and bone conduction thresholds or with APHAB score. Bonebridge implantation is beneficial to patients with CHL or MHL, or with SSD. Assessment of patients for Bonebridge implantation is complex, and audiometric data should be complemented by patient-reported outcomes to provide deeper insight into their individual needs and attitudes.