Miracle-dz/UniFAR-FTUs huggingface dataset:
Shh pathway activation is present and required within the vertebrate limb bud apical ectodermal ridge for normal autopod patterning

Expression of Sonic Hedgehog (Shh) in the posterior mesenchyme of the developing limb bud regulates patterning and growth of the developing limb by activation of the Hedgehog (Hh) signaling pathway. Through the analysis of Shh and Hh signaling target genes, it has been shown that activation in the limb bud mesoderm is required for normal limb development to occur. In contrast, it has been stated that Hh signaling in the limb bud ectoderm cannot occur because components of the Hh signaling pathway and Hh target genes have not been found in this tissue. However, recent array-based data identified both the components necessary to activate the Hh signaling pathway and targets of this pathway in the limb bud ectoderm. Using immunohistochemistry and various methods of detection for targets of Hh signaling, we found that SHH protein and targets of Hh signaling are present in the limb bud ectoderm including the apex of the bud. To directly test whether ectodermal Hh signaling was required for normal limb patterning, we removed Smo, an essential component of the Hh signaling pathway, from the apical ectodermal ridge (AER). Loss of functional Hh signaling in the AER resulted in disruption of the normal digit pattern and formation of additional postaxial cartilaginous condensations. These data indicate that contrary to previous accounts, the Hh signaling pathway is present and required in the developing limb AER for normal autopod development.
The influence of facility design and human resource management on health care professionals.

BACKGROUND Cost control of health care services is a strategic concern for organizations. To lower costs, some organizations reduce staffing levels. However, this may not be worth the trade-off, as the quality of services will likely be reduced, morale among health care providers tends to suffer, and patient satisfaction is likely to decline. PURPOSE The potential synergy between human resource management and facility design and operation was investigated to achieve the goal of providing cost containment strategies without sacrificing the quality of services and the commitment of employees. METHODOLOGY About 700 health care professionals from 10 acute-care hospitals participated in this cross-sectional study. The authors used structural equation modeling to test whether employees' evaluations of their physical work environment and human resource practices were significantly associated with lower job-related anxiety, higher job satisfaction, and higher organizational commitment. FINDINGS The analysis found that employees' evaluations of their physical work environment and human resource practices influenced their job-related feelings and attitudes. Perceived organizational support mediated this relationship. The study also found a small but positive interaction effect between the physical work environment and human resource practices. The influence of physical work environment was small, mainly because of the high predictive value of human resource practices and strong confounding variables included in the analysis. This study specifically showed the role of facility design in reducing job-related anxiety among caregivers. PRACTICE IMPLICATIONS Preliminary evidence is provided that facility design can be used as a managerial tool for improving job-related attitudes and feelings of employees and earning their commitment. Providing a healthy and safe work environment can be perceived by employees as an indication that the organization respects them and cares about their well-being, which might be reciprocated with higher levels of motivation and commitment toward the organization.
A Perspective on the Application of Spatially Resolved ARPES for 2D Materials

In this paper, a perspective on the application of Spatially- and Angle-Resolved PhotoEmission Spectroscopy (ARPES) for the study of two-dimensional (2D) materials is presented. ARPES allows the direct measurement of the electronic band structure of materials generating extremely useful insights into their electronic properties. The possibility to apply this technique to 2D materials is of paramount importance because these ultrathin layers are considered fundamental for future electronic, photonic and spintronic devices. In this review an overview of the technical aspects of spatially localized ARPES is given along with a description of the most advanced setups for laboratory and synchrotron-based equipment. This technique is sensitive to the lateral dimensions of the sample. Therefore, a discussion on the preparation methods of 2D material is presented. Some of the most interesting results obtained by ARPES are reported in three sections including: graphene, transition metal dichalcogenides (TMDCs) and 2D heterostructures. Graphene has played a key role in ARPES studies because it inspired the use of this technique with other 2D materials. TMDCs are presented for their peculiar transport, optical and spin properties. Finally, the section featuring heterostructures highlights a future direction for research into 2D material structures.
Reevaluation of ATR signaling in primary resting chronic lymphocytic leukemia cells: evidence for pro-survival or pro-apoptotic function

ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53. Similar results were obtained with the purine analogs fludarabine and cladribine that were also shown to activate ATR and induce ATR-dependent phosphorylation of H2AX and p53. In addition, ATR inhibition was found to sensitize primary CLL cells to UV-C by decreasing DNA repair synthesis. Conversely, ATR inhibition rescued CLL cells against purine analogs by reducing expression of the pro-apoptotic genes PUMA and BAX. Collectively, our study indicates that ATR signaling can be activated in resting CLL cells and play a pro-survival or pro-apoptotic role, depending on the genotoxic context.
Neuromedin B Expression Defines the Mouse Retrotrapezoid Nucleus

The retrotrapezoid nucleus (RTN) consists, by definition, of Phox2b-expressing, glutamatergic, non-catecholaminergic, noncholinergic neurons located in the parafacial region of the medulla oblongata. An unknown proportion of RTN neurons are central respiratory chemoreceptors and there is mounting evidence for biochemical diversity among these cells. Here, we used multiplexed in situ hybridization and single-cell RNA-Seq in male and female mice to provide a more comprehensive view of the phenotypic diversity of RTN neurons. We now demonstrate that the RTN of mice can be identified with a single and specific marker, Neuromedin B mRNA (Nmb). Most (∼75%) RTN neurons express low-to-moderate levels of Nmb and display chemoreceptor properties. Namely they are activated by hypercapnia, but not by hypoxia, and express proton sensors, TASK-2 and Gpr4. These Nmb-low RTN neurons also express varying levels of transcripts for Gal, Penk, and Adcyap1, and receptors for substance P, orexin, serotonin, and ATP. A subset of RTN neurons (∼20–25%), typically larger than average, express very high levels of Nmb mRNA. These Nmb-high RTN neurons do not express Fos after hypercapnia and have low-to-undetectable levels of Kcnk5 or Gpr4 transcripts; they also express Adcyap1, but are essentially devoid of Penk and Gal transcripts. In male rats, Nmb is also a marker of the RTN but, unlike in mice, this gene is expressed by other types of nearby neurons located within the ventromedial medulla. In sum, Nmb is a selective marker of the RTN in rodents; Nmb-low neurons, the vast majority, are central respiratory chemoreceptors, whereas Nmb-high neurons likely have other functions. SIGNIFICANCE STATEMENT Central respiratory chemoreceptors regulate arterial PCO2 by adjusting lung ventilation. Such cells have recently been identified within the retrotrapezoid nucleus (RTN), a brainstem nucleus defined by genetic lineage and a cumbersome combination of markers. Using single-cell RNA-Seq and multiplexed in situ hybridization, we show here that a single marker, Neuromedin B mRNA (Nmb), identifies RTN neurons in rodents. We also suggest that >75% of these Nmb neurons are chemoreceptors because they are strongly activated by hypercapnia and express high levels of proton sensors (Kcnk5 and Gpr4). The other RTN neurons express very high levels of Nmb, but low levels of Kcnk5/Gpr4/pre-pro-galanin/pre-pro-enkephalin, and do not respond to hypercapnia. Their function is unknown.
HtrA1 Is Specifically Up-Regulated in Active Keloid Lesions and Stimulates Keloid Development

Keloids occur after failure of the wound healing process; inflammation persists, and various treatments are ineffective. Keloid pathogenesis is still unclear. We have previously analysed the gene expression profiles in keloid tissue and found that HtrA1 was markedly up-regulated in the keloid lesions. HtrA1 is a serine protease suggested to play a role in the pathogenesis of various diseases, including age-related macular degeneration and osteoarthritis, by modulating extracellular matrix or cell surface proteins. We analysed HtrA1 localization and its role in keloid pathogenesis. Thirty keloid patients and twelve unrelated patients were enrolled for in situ hybridization, immunohistochemical, western blot, and cell proliferation analyses. Fibroblast-like cells expressed more HtrA1 in active keloid lesions than in surrounding lesions. The proportion of HtrA1-positive cells in keloids was significantly higher than that in normal skin, and HtrA1 protein was up-regulated relative to normal skin. Silencing HtrA1 gene expression significantly suppressed cell proliferation. HtrA1 was highly expressed in keloid tissues, and the suppression of the HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development by accelerating cell proliferation and remodelling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.
Causes of reduced leaf‐level photosynthesis during strong El Niño drought in a Central Amazon forest

Sustained drought and concomitant high temperature may reduce photosynthesis and cause tree mortality. Possible causes of reduced photosynthesis include stomatal closure and biochemical inhibition, but their relative roles are unknown in Amazon trees during strong drought events. We assessed the effects of the recent (2015) strong El Niño drought on leaf‐level photosynthesis of Central Amazon trees via these two mechanisms. Through four seasons of 2015, we measured leaf gas exchange, chlorophyll a fluorescence parameters, chlorophyll concentration, and nutrient content in leaves of 57 upper canopy and understory trees of a lowland terra firme forest on well‐drained infertile oxisol. Photosynthesis decreased 28% in the upper canopy and 17% in understory trees during the extreme dry season of 2015, relative to other 2015 seasons and was also lower than the climatically normal dry season of the following non‐El Niño year. Photosynthesis reduction under extreme drought and high temperature in the 2015 dry season was related only to stomatal closure in both upper canopy and understory trees, and not to chlorophyll a fluorescence parameters, chlorophyll, or leaf nutrient concentration. The distinction is important because stomatal closure is a transient regulatory response that can reverse when water becomes available, whereas the other responses reflect more permanent changes or damage to the photosynthetic apparatus. Photosynthesis decrease due to stomatal closure during the 2015 extreme dry season was followed 2 months later by an increase in photosynthesis as rains returned, indicating a margin of resilience to one‐off extreme climatic events in Amazonian forests.
Retinal nerve fiber layer thickness changes in patients with age-related macular degeneration treated with intravitreal ranibizumab.

PURPOSE To assess the effects of intravitreal ranibizumab therapy on intraocular pressure (IOP) and retinal nerve fiber (RNFL) thickness. METHODS Forty-nine eyes of 49 patients with neovascular age-related macular degeneration (AMD) treated with intravitreal ranibizumab injections and 27 fellow eyes not requiring treatment were followed for 1 year. RNFL thickness, as measured by Fourier domain optical coherence tomography, and IOP were determined pre- and postinjection. RESULTS After 12 months, the mean number of injections received was 4.8 ± 1.6. The incidence of IOP elevations (>5 mm Hg over baseline) observed at the time of injection was 0.4%. Baseline RNFL thickness was 105.7 ± 12.2 μm in the treatment group compared with 101.8 ± 11.6 μm in the control group (P = 0.176). At the end of follow-up, significant RNFL thinning was noted in the treatment group (100.2 ± 11.0 μm, P < 0.001), whereas no differences were found in the control group (100.5 ± 10.8 μm, P = 0.477). CONCLUSIONS Intravitreal ranibizumab injections used to treat AMD caused a significant change in RNFL thickness after 12 months of follow-up.
Quantitative investigation of nuclear morphology in glioblastomas and its relation to survival time.

OBJECTIVE To investigate the influence of nuclear morphology of tumor cells on survival time of patients with primary glioblastomas. STUDY DESIGN Tumor cell nuclei have been measured in paraffin sections from 51 glioblastomas (Ki-67 immunostaining). In each tumor, the region with the highest proliferative activity has been selected for performing the morphometric analysis. Nuclear area, shape variables (roundness factor, Fourier amplitudes) and the proliferation index Ki-67 have been determined. Statistical relationships between these variables have been tested by principal component analysis and Spearman's correlation analysis. The survival time has been tested using Kaplan-Meier analysis. The influence of morphometric variables on survival time and on the time until recurrence has been tested by Cox analysis. RESULTS There is a significant correlation of mean value and standard deviation of nuclear area with shape variables. Cox analysis showed a significant influence of the quantitative morphologic variables on survival time for patients with and without complete surgical resection. For patients with complete surgical resection, there was a distinct influence of mean nuclear area on survival time. Patients with incomplete surgical resection of the tumors had a significantly shorter survival. No significant influence of the variables on the time from surgery to recurrence could be shown. CONCLUSION Quantitative morphology of tumor cell nuclei in our set of glioblastoma cases showed a statistically significant relation with the survival time of the patients, indicating the biological significance of nuclear morphology in glioblastomas.
Expression of nitric oxide synthase in ulcerative colitis

Abstract. Nitric oxide (NO) is generated from L‐arginine by a family of enzymes called the NO synthases. Previous investigators have proposed that the expression of this inducible enzyme (iNOS) may account for the characteristic vasodilatation, oedema and impairment of gut motility seen in active ulcerative colitis. Using a specific antibody to iNOS, we have investigated the distribution of this enzyme in colonic tissue from patients with histologically proven ulcerative colitis. Eight patients with ulcerative colitis expressed calcium‐independent citrulline activity (9.96±2.34 pmol citrulline mg‐1 protein min‐1) and showed immunoreactivity to the iNOS antibody within the inflammatory infiltrate of the lamina propria, and also within the cytoplasm of the epithelial cells lining the colon. Five age‐matched controls showed no calcium‐independent citrulline activity (0.2 ±0.08 pmol citrulline mg‐1 protein min‐1) and no immunoreaction to the antibody. We conclude that this enzyme is present in colonic tissue including the epithelium from patients with active colitis. Inhibition of this enzyme may provide a novel therapeutic option for patients with active ulcerative colitis.
Development and Analysis of an Electrically Activated Sucker for Handling Workpieces With Rough and Uneven Surfaces

In this study, we designed an electrically activated sucker that can handle workpieces with rough and uneven surfaces. The new sucker uses a motor to drive its blades to form a rotational flow in a shell, generating a cupped negative pressure distribution and a resulting suction force F. Unlike in existing suckers, the rotational flow in the new sucker is formed close to the upper surface of the workpiece and extends to the outermost region of the shell. There is no air inlet or outlet in the space enclosed by the workpiece and the shell and, thus, no inlet or outlet flow is caused. This design solves the traditional problem of vacuum leak, maintains the suction force even for workpieces with rough and uneven surfaces, and works with little energy consumption. Through theoretical analysis and experiments, we studied the key parameters, i.e., the rotational speed ω and inner radius R2 of the shell, and clarified the relationships of F-ω and F-R2. We also investigated the effect of the driving torque, energy consumption, and surface state on the suction force. Furthermore, we used the new sucker to pick up several types of workpieces to confirm its applicability. Finally, we compared the force-energy ratio and force-area ratio of the new sucker with existing suckers and confirmed that the new sucker is superior in terms of force-energy ratio but is inferior in terms of force-area ratio.
Latent trajectories of internalizing symptoms from preschool to school age: A multi-informant study in a high-risk sample

Abstract Recent proposals suggest early adversity sets in motion particularly chronic and neurobiologically distinct trajectories of internalizing symptoms. However, few prospective studies in high-risk samples delineate distinct trajectories of internalizing symptoms from preschool age onward. We examined trajectories in a high-risk cohort, oversampled for internalizing symptoms, several preschool risk/maintenance factors, and school-age outcomes. Parents of 325 children completed the Strengths and Difficulties Questionnaire on up to four waves of data collection from preschool (3–5 years) to school age (8–9 years) and Preschool Age Psychiatric Assessment interviews at both ages. Multi-informant data were collected on risk factors and symptoms. Growth mixture modelling identified four trajectory classes of internalizing symptoms with stable low, rising low-to-moderate, stable moderate, and stable high symptoms. Children in the stable high symptom trajectory manifested clinically relevant internalizing symptoms, mainly diagnosed with anxiety disorders/depression at preschool and school age. Trajectories differed regarding loss/separation experience, maltreatment, maternal psychopathology, temperament, and stress-hormone regulation with loss/separation, temperament, maternal psychopathology, and stress-hormone regulation (trend) significantly contributing to explained variance. At school age, trajectories continued to differ on symptoms, disorders, and impairment. Our study is among the first to show that severe early adversity may trigger a chronic and neurobiologically distinct internalizing trajectory from preschool age onward.
Reflections on the Use of a Personal Response System (PRS) for Summative Assessment in an Undergraduate Taught Module

This paper outlines the authorâs experience of using a Personal Response System (PRS) for summative assessment in a 3rd year undergraduate taught module, over a 2 year period. The rationale for implementation of this method of assessment was a relatively high failure rate in the previous written examination (37%), and to reduce the marking burden for the teaching team. Key challenges identified with the implementation of the assessment process were reliability of the hardware/software, and student and staff confidence with the PRS and assessment process. Following the introduction of the new assessment method, the assessment failure rate was reduced to 9%. The PRS was seen as a good tool for summative assessment and received very positive student feedback comments. The PRS proved to be reliable, and with support and guidance, both students and staff felt confident with the process.
Temperature-Driven Local Acclimatization of Symbiodnium Hosted by the Coral Galaxea fascicularis at Hainan Island, China

The success of coral reef ecosystems largely depends on mutualistic symbiosis between scleractinian corals and the dinoflagellate photosymbiont Symbiodinium spp. However, further investigation is needed to elucidate the flexibility of coral-algae associations in response to environmental changes. In this study, we applied a molecular method (high-throughput internal transcribed spacer 2 region of ribosomal RNA gene amplicon sequencing) to explore diversity and flexibility of Symbiodinium associated with Galaxea fascicularis, an ecologically important scleractinian coral species collected at five locations around Hainan Island, South China Sea. The results revealed a high diversity of Symbiodinium subclades with C2r and D17 being dominant in G. fascicularis. Clade D Symbiodinium occurred most frequently in habitats where the annual average sea surface temperatures are the highest, suggesting that temperature is an important factor in determining Symbiodinium D abundance in G. fascicularis. The distribution of coral-Symbiodinium associations are possibly mediated by trade-off mechanisms which change the relative abundance of Symbiodinium clades/subclades under different environmental conditions. These findings provide further evidence that reef-building corals such as G. fascicularis can shuffle their symbionts to cope with environmental changes, and have implications for our understanding of the ecology of flexible coral-algal symbiosis.