Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequency–dependency of the involvement of dopamine D1/D5 and beta‐adrenergic receptors in hippocampal LTD triggered by locus coeruleus stimulation

Patterned stimulation of the locus coeruleus (LC, 100 Hz), in conjunction with test‐pulse stimulation of hippocampal afferents, results in input‐specific long‐term depression (LTD) of synaptic plasticity in the hippocampus. Effects are long‐lasting and have been described in Schaffer‐collateral–CA1 and perforant path‐dentate gyrus synapses in behaving rats. To what extent LC‐mediated hippocampal LTD (LC‐LTD) is frequency‐dependent is unclear. Here, we report that LC‐LTD can be triggered by LC stimulation with 2 and 5 Hz akin to tonic activity, 10 Hz equivalent to phasic activity, and 100 Hz akin to high‐phasic activity in the dentate gyrus (DG) of freely behaving rats. LC‐LTD at both 2 and 100 Hz can be significantly prevented by an NMDA receptor antagonist. The LC releases both noradrenaline (NA) and dopamine (DA) from its hippocampal terminals and may also trigger hippocampal DA release by activating the ventral tegmental area (VTA). Unclear is whether both neurotransmitters contribute equally to hippocampal LTD triggered by LC stimulation (LC‐LTD). Both DA D1/D5 receptors (D1/D5R) and beta‐adrenergic receptors (β‐AR) are critically required for hippocampal LTD that is induced by patterned stimulation of hippocampal afferents, or is facilitated by spatial learning. We, therefore, explored to what extent these receptor subtypes mediate frequency‐dependent hippocampal LC‐LTD. LC‐LTD elicited by 2, 5, and 10 Hz stimulation was unaffected by antagonism of β‐AR with propranolol, whereas LC‐LTD induced by these frequencies was prevented by D1/D5R‐antagonism using SCH23390. By contrast, LC‐LTD evoked at 100 Hz was prevented by β‐AR‐antagonism and only mildly affected by D1/D5R‐antagonism. Taken together, these findings support that LC‐LTD can be triggered by LC activity at a wide range of frequencies. Furthermore, the contribution of D1/D5R and β‐AR to hippocampal LTD that is triggered by LC activity is frequency‐dependent and suggests that D1/D5R may be involved in LC‐mediated hippocampal tonus.
Idiopathic Epiretinal Membranes: Visual Outcomes and Prognostic Factors

Objectives: To evaluate the associations between anatomical changes and visual outcomes in patients with idiopathic epiretinal membrane (ERM). Materials and Methods: We performed a prospective study of 130 consecutive idiopathic ERM patients and report their visual outcomes and the factors associated with visual outcome and anatomical changes. Results: Of 130 eyes of 130 patients, 87 eyes underwent surgery, while the remaining 43 eyes were observed. At 6-month follow-up, the best-corrected visual acuity (BCVA) increased in the whole population. Mean Early Treatment Diabetic Retinopathy Study letter score changed from 51 to 65 in the surgical group and from 67 to 68 in the non-surgical group. The surgical group had improvement in BCVA at all ERM stages and grades of disorganization of the retinal inner layers (DRIL) (p<0.01). In multivariable analysis of the surgical group, factors associated with BCVA of ETDRS 60 letters or more were no or mild DRIL and the absence of ellipsoid zone disruption at baseline (p=0.002 and p=0.034, respectively) and this statistically significant positive correlation was still maintained at 12-month follow-up. Conclusion: Baseline DRIL grade and presence of ellipsoid zone disruption were the most informative prognostic factors in patients with idiopathic ERMs. Patients with severe DRIL and/or advanced ERMs had improved vision after ERM removal.
Misfolded GBA/β-glucocerebrosidase impairs ER-quality control by chaperone-mediated autophagy in Parkinson disease

ABSTRACT Inhibition of chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation for intracellular proteins, may contribute to pathogenesis in neurodegenerative diseases including Parkinson disease (PD). Pathogenic variants of PD-related proteins that reside in the cytosol, including SNCA/alpha-synuclein, LRRK2 (leucine rich repeat kinase 2), UCHL1 (ubiquitin Cterminal hydrolase 1) and VPS35 (VPS35 retromer complex component), exert inhibitory effects on CMA. Decreased CMA activity has also been reported in sporadic PD patients, consistent with an association between CMA inhibition and PD. We have now reported the first example of CMA dysfunction caused by a non-cytosolic PD-related protein, GBA/β-glucocerebrosidase, the most common genetic risk factor for PD, which uncovers a new role for CMA in endoplasmic reticulum (ER) quality control.
Potential clinical value of in vitro spermatogenesis

Abstract Infertility has become the third most common disease threatening human health, immediately after tumors and cardiovascular diseases. Male infertility is primarily caused by spermatogenesis disorders that may be classified as either genetic or non-genetic. For part of non-genetic disorders, in vitro spermatogenesis can be induced by adjusting the microenvironment of the testis culture. Establishing the in vitro spermatogenic induction system helps to clarify the critical molecular mechanisms in spermatogonia self-renewal, spermatocyte meiosis, and sperm formation during spermatogenesis. In this review, we summarize recent advances in the field of in vitro sperm cells induction. Therefore, we hope to provide ideas and solutions for the clinical treatment of male infertility. Summary Sentence This review provides recent advances in the field of in vitro sperm cells induction and discusses potential clinical value of in vitro spermatogenesis. Graphical Abstract
Evaluation of the effects of disulfiram, an alcohol-aversive agent with anti-cancer activity, on mouse bone marrow cells

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.
Large and expensive brain comes with a short lifespan: The relationship between brain size and longevity among fish taxa

Abstract Vertebrates show substantial interspecific variation in brain size in relation to body mass. It has long been recognized that the evolution of large brains is associated with both costs and benefits, and it is their net benefit which should be favoured by natural selection. On one hand, the substantial energetic cost imposed by the maintenance of neural tissue is expected to compromise the energetic budget of organisms with large brains and their investment in other critical organs (expensive brain framework, EBF) or important physiological process, such as somatic maintenance and repair, thus accelerating ageing that shortens lifespan, as predicted by the disposable soma theory (DST). However, selection towards larger brain size can provide cognitive benefits (e.g., high behavioural flexibility) that may mitigate extrinsic mortality pressures, and thus may indirectly select for slower ageing that prolongs lifespan, as predicted by the cognitive buffer hypothesis (CBH). The relationship between longevity and brain size has been investigated to date only among terrestrial vertebrates, although the same selective forces acting on those species may also affect vertebrates living in aquatic habitats, such as fish. Thus, whether this evolutionary trade‐off for brain size and longevity exists on a large scale among fish clades remains to be addressed. In this study, using a global dataset of 407 fish species, I undertook the first phylogenetic test of the brain size/longevity relationship in aquatic vertebrate species. The study revealed a negative relationship between brain size and longevity among cartilaginous fish confirming EBF and DST. However, no pattern emerged among bony fish species. Among sharks and rays, the high metabolic cost of producing neural tissue transcends the cognitive benefits of evolving a larger brain. Consequently, my findings suggest that the cost of maintaining brain tissue is relatively higher in ectothermic species than in endothermic ones.
Effectiveness of a psychological growth camp without internet in the treatment of adolescents at risk of internet addiction: a pilot study

Abstract Objective This study aimed to investigate the effects of a psychological growth camp in the treatment of adolescents at risk of Internet addiction in Taiwan. Methods We designed a psychological growth camp to treat adolescents at risk of Internet addiction. The CIAS (Chen Internet Addiction Scale) was used to assess the severity of Internet addiction at baseline, immediately after the camp, and at 1-month and 2-month follow-up visits. Results A total of 16 participants were recruited, including 10 at risk of Internet addiction and 6 without the risk of Internet addiction. The results indicated that the participants not in a 2-parent family had significantly higher CIAS scores than those in a 2-parent family (p = .034). The participants at risk of Internet addiction exhibited significant improvements in total CIAS score at the time immediately after the camp (p = .033) and at 1-month (p = .001) and 2-month (p = .003) follow-up visits. Moreover, the incidence of possible Internet addiction was not significantly decreased immediately after the camp (p = .056) but was significantly decreased at 1- and 2-month follow-up visits (p < .05) compared with the baseline level. Otherwise, no significant improvements in total CIAS score or subscales were observed at the follow-up visits (p > .05) for the participants not at risk of Internet addiction. Conclusion The results indicate that the psychological growth camp without Internet might be effective in treating adolescents with Internet addiction.
Retrospective analysis of 302 ovine dystocia cases presented to a veterinary hospital with particular attention to uterine torsion

Abstract Background Dystocia is common in sheep, and foetal causes are predominant. Among maternal causes, insufficient cervical dilatation is the most frequent problem. Uterine torsion has been considered rare by many authors. Objectives This study was conducted to investigate causes of dystocia in sheep presented for veterinary attention, and particular focus was set on the description of uterine torsion and analysis of potentially predisposing factors for this condition. Methods Clinical records of 302 sheep treated for dystocia were evaluated retrospectively. Known and proposed risk factors for uterine torsion in cattle were analysed regarding their potential importance in sheep. These included lamb birth weights, ewe age, parity, season, nutrition, breed type, litter size and husbandry. Results Maternal causes of dystocia accounted for 67.2% (203/302) of the presented cases. Of these, insufficient cervical dilatation (121/203, 59.6%) was the most frequent diagnosis. Another substantial proportion of maternal causes (60/203, 29.6%) was identified as uterine torsion. Husbandry, breed type and litter size showed significance in univariate analyses, with lower odds for meat breeds (OR 0.22; p < 0.001), twin‐ (OR 0.49; p = 0.020) or multiple‐bearing ewes (OR 0.19; p = 0.013) and higher odds for fully housed animals (OR 17.87; p < 0.001). Year‐round housing was identified as the most influential factor in a subsequent multivariate analysis. Conclusions Uterine torsion was identified as a relevant cause of dystocia in our case load. The condition is likely to be underdiagnosed in sheep, and increased farmer and veterinary awareness is necessary to ensure adequate treatment of affected animals and to prevent unnecessary suffering.
Evidence of latent HPV infection in older Danish women with a previous history of cervical dysplasia

Understanding whether human papillomavirus (HPV) may establish latency in the uterine cervix is important. A better understanding of HPV natural history is useful for clinical counseling of women attending screening and to accurately inform health prevention strategies such as screening and HPV vaccination. We evaluated the extent of latent HPV infections in older women with a history of abnormal cytology.
Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion

Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder frequently associated with mutations in NIPBL. CdLS is thought to arise from developmental gene regulation defects, but how NIPBL mutations cause these is unknown. Here we show that several NIPBL mutations impair the DNA loop extrusion activity of cohesin. Because this activity is required for the formation of chromatin loops and topologically associating domains, which have important roles in gene regulation, our results suggest that defects in cohesin-mediated loop extrusion contribute to the etiology of CdLS by altering interactions between developmental genes and their enhancers.
Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer

Significance Pancreatic cancer is a leading cause of cancer-related death, in part due to incomplete responses to standard-of-care chemotherapy. In this study, using a combination of single-cell RNA sequencing and high-throughput proteomics, we identified the calcium-responsive protein calmodulin as a key mediator of resistance to the first-line chemotherapy agent gemcitabine. Inhibition of calmodulin led to the loss of gemcitabine resistance in vitro, which was recapitulated using a calcium chelator or Food and Drug Administration–approved calcium channel blockers (CCBs), including amlodipine. In animal studies, amlodipine markedly enhanced therapeutic responses to gemcitabine chemotherapy, reducing the incidence of distant metastases and extending survival. Hence, incorporating CCBs may provide a safe and effective means of improving responses to gemcitabine-based chemotherapy in pancreatic cancer patients.
Qualitative assessment of an immersive teleoperation environment for collaborative professional activities in a "beaming" experiment

The current study assesses an immersive teleoperation platform for professional collaborative activities. Thisplatform uses an iCub robot and virtual-reality hardware (VR headset and motion capture) to elicit an embodimentsituation, where the pilot collaborates with remote actors through the robot ("beaming platform"): through therobot, the pilot can act and perceive using his natural affordances (head moving, vision and hearing) that aremapped to/from the robot effectors/sensors. One challenge is to measure how the robot expression capacity levelcan modulate the efficiency of the participation of the remote pilot with his collaborators. An experience wherethe pilot trains two subjects to assemble a mechanical system was organised: we observed the capacity of the twosubjects to realize the task they discover and to collaborate with the pilot, with a more or less expressive robot.This experience clearly highlighted the importance of embodiment and the opportunities opened by beamingplatforms, allowing the enhancement of the physical space by agents:i.e. social robots or conversational agents.
Epstein-Barr Virus Latent Membrane Protein 1 Genetic Variability in Peripheral Blood B Cells and Oropharyngeal Fluids

ABSTRACT We report the diversity of latent membrane protein 1 (LMP1) gene founder sequences and the level of Epstein-Barr virus (EBV) genome variability over time and across anatomic compartments by using virus genomes amplified directly from oropharyngeal wash specimens and peripheral blood B cells during acute infection and convalescence. The intrahost nucleotide variability of the founder virus was 0.02% across the region sequences, and diversity increased significantly over time in the oropharyngeal compartment (P = 0.004). The LMP1 region showing the greatest level of variability in both compartments, and over time, was concentrated within the functional carboxyl-terminal activating regions 2 and 3 (CTAR2 and CTAR3). Interestingly, a deletion in a proline-rich repeat region (amino acids 274 to 289) of EBV commonly reported in EBV sequenced from cancer specimens was not observed in acute infectious mononucleosis (AIM) patients. Taken together, these data highlight the diversity in circulating EBV genomes and its potential importance in disease pathogenesis and vaccine design. IMPORTANCE This study is among the first to leverage an improved high-throughput deep-sequencing methodology to investigate directly from patient samples the degree of diversity in Epstein-Barr virus (EBV) populations and the extent to which viral genome diversity develops over time in the infected host. Significant variability of circulating EBV latent membrane protein 1 (LMP1) gene sequences was observed between cellular and oral wash samples, and this variability increased over time in oral wash samples. The significance of EBV genetic diversity in transmission and disease pathogenesis are discussed.
Song as a signal of male identity and quality in the Green-winged Saltator (Saltator similis)

ABSTRACT Birdsong is commonly associated with sexual selection. It can influence mate choice through honestly signaling the emitter's quality. Such quality may be reflected, among other factors, in body condition and bite force. The Green-winged Saltator (Saltator similis) is a good model species to assess such relationships because males defend their territories throughout the year and sing a stereotyped song, which is known to be associated with sexual selection. The objective of this work is to assess the relationships among song structure, vocal individuality, and possible fitness indicators (body condition, morphology, and bite force) in captive male Green-winged Saltators. We conducted a linear discriminant analysis (LDA) to assess vocal individuality and to highlight the principal acoustic variables associated with it. We conducted Y-Aware PCAs to evaluate the relationship between the body condition index, bite force, and morphometric and bioacoustic variables. The morphometric variables, particularly head width and length, explained 23% of the bite force variation. The acoustic variation explained 36.17% of body condition index variation, but a small nonsignificant amount of bite force (12%). From the acoustic variables, peak frequency and high frequency of the last syllable, slope of the first syllable, and emission rate showed significant negative relationships with body condition. The LDA model based on acoustic variables had a 97.47% accuracy, although this result might also reflect regional song dialects. The acoustic variables most relevant to individual classification (first syllable duration, last syllable duration, whole-song slope, and whole-song duration) are not the same variables that had a stronger relationship to body condition. Besides that, there can be a weaker mixed signaling, as variables related to frequency modulations were important in both contexts. Our results suggest that the song may act as an honest signal of an individual's body condition in this species.
New Framework for Evaluating Ecosystem Quality in Nature Reserves based on Ideal References and Key Indicators

Abstract: With increasing numbers and types of nature reserves (NRs), objective evaluation and comparison of the effects of different nature NRs on conservation efforts are of great importance for protecting species diversity, ensuring reasonable national economic input, and adjusting government management schemes. Developing a method for the combined assessment of flagship or umbrella species and ecosystem quality will improve the evaluation of NRs. However, it is also important to establish a new framework for rapid evaluation of ecosystem quality, supported by the advantages of scientific, economic, and regular principles. Here, we proposed a new framework that incorporates the novel concept of ideal references into evaluation systems, which will facilitate the comparison of results from different periods and regions. Furthermore, from the perspective of making the framework as objective, rapid, and economical as possible, we recommended some key ecological indicators, such as net primary productivity, soil organic matter, plant diversity, for use in the new evaluation framework. The new framework, referred to as “ideal reference and key indicators” (IRKI), can sufficiently meet the requirements for the rapid evaluation of ecosystem quality both regionally and nationally. Furthermore, IRKI can identify the restoration potential and restoration periods of NRs, thus facilitating the rational distribution of resources and enhancing the protective effect. There are many types of NRs in China, and it is necessary to partially alter the assessment methods or parameters for different types of NRs. Overall, IRKI provides a simple, clear, and comparable framework that will strongly enhance the conservation of protected areas (PAs) and facilitate the standardization of management practices.
Spatial Patterns of Soil Organic Matter, Nitrogen, Phosphorus and Potassium in a Subtropical Forest and Its Implication for Forest Management

Abstract: Total nitrogen (TN), total phosphorus (TP), total potassium (TK), and soil organic matter (OM) can significantly affect forest growth. However, these soil properties are spatially heterogeneously distributed, complicating the prescription of forest management strategies. Thus, it is imperative to obtain an in-depth understanding of the spatial distribution of soil properties. In this study, soils were sampled at 181 locations in the Tropical Forest Research Center in the southwestern Guangxi Zhuang Autonomous Region in southern China. We investigated the spatial variability of soil OM, TN, TP, and TK using geostatistical analysis. The nugget to sill ratio indicated a strong spatial dependence of soil TN and a moderate spatial dependence of soil OM, TP, and TK, suggesting that TN was primarily controlled by intrinsic factors (e.g., soil texture, parent material, vegetation type, and topography), whereas soil OM, TP, and TK were controlled by intrinsic and extrinsic factors (e.g., cultivation practices, fertilization, and planting systems). Based on the spatial variability determined by the geostatistical analysis, we performed ordinary kriging to create thematic maps of soil TN, TP, TK, and OM. Model validation indicated that the thematic maps were reliable to inform forest management.