Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuronal-specific function of hTim8a in Complex IV assembly provides insight into the molecular mechanism underlying Mohr-Tranebjærg syndrome

Human Tim8a is a member of an intermembrane space chaperone network, known as the small TIM family, which transport hydrophobic membrane proteins through this compartment. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells and consequently how lack of hTim8a leads to a neurodegenerative disease. We identified a novel cell-specific function of hTim8a in the assembly of Complex IV, which is mediated through a transient interaction with the copper chaperone COX17. Complex IV assembly defects in cells lacking hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c and Bax, which primes cells for cell death. Alleviation of oxidative stress using Vitamin E rescues cells from apoptotic vulnerability. We hypothesis that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.
Evaluation of Red Cell Distribution Width to Lymphocyte Ratio as Potential Biomarker for Detection of Colorectal Cancer

Background and Aim Colorectal cancer (CRC) is the third most lethal cancer globally. This study sought to determine the feasibility of using red cell distribution width-to-lymphocyte ratio (RLR) as a tool to facilitate CRC detection. Methods Seventy-eight healthy controls, 162 patients diagnosed with CRC, and 94 patients with colorectal polyps (CP) from June 2017 to October 2018 were retrospectively reviewed. Clinical data were obtained to analyze preoperative RLR level, and receiver operating characteristic (ROC) curve analysis was performed to estimate the potential role of RLR as a CRC biomarker. Results RLR was higher in patients with CRC than in healthy participants (P < 0.05). ROC analysis indicated that combined detection of RLR and CEA appears to be a more effective marker to distinguish among controls, CP, and CRC patients, yielding 56% sensitivity and 90% specificity. RLR levels were significantly greater in those who had more advanced TNM stages (P < 0.05) and patients with distant metastasis stages (P < 0.05). Conclusions RLR might serve as a potential biomarker for CRC diagnosis.
Effects of Teucrium polium L. (Lamiaceae) essential oil and α-pinene on the detoxifying- and intermediary engaged enzymes of Ephestia kuehniella Zeller, 1879 (Lep.: Pyralidae)

<p>This study investigated the effect of <em>Teucrium polium</em> L. essential oil (<em>Tp</em> EO) and α-pinene as its major component on the detoxifying- and intermediary-engaged enzymes of <em>Ephestia kuehniella</em> Zeller. Fourth instar larvae were separately fed on the treated artificial diets incorporated with LC<sub>50</sub> concentration of <em>Tp</em> EO (4.91 μl ml<sup>-1</sup>) and α-pinene (10.66 μl ml<sup>-1</sup>). After three time intervals (24, 48, 72 hours), larval hemolymph was extracted to determine enzymatic activities. Activity of esterase, alanine and aspartate aminotransferases, aldolase, lactate dehydrogenase, and alkaline phosphatase were decreased in the treatments compared with the control. No significant differences were observed between some enzymes in the treated larvae highlighting their ineffectively role to detoxify and to metabolize <em>Tp</em> EO<em> </em>and α-pinene in the hemolyph of <em>E. kuehniella</em> larvae. </p>
Different responses but complementary views: patterns of cross-taxa diversity under contrasting coastal dynamics in secondary sand dunes

Abstract Coastal sand dunes are dynamic ecosystems, with vegetation and biota responding to continuous changes in its typical environmental severity. Understanding vegetation patterns is relevant to early detect shifts in prevailing coastal dynamics and to refine monitoring strategies, especially in secondary sand dunes, which are under legal protection in Europe. We assessed the diversity patterns and cross-taxa congruence among lichens, bryophytes and vascular plants in secondary sand dunes under contrasting coastal dynamics (i.e. stable versus erosion sites), along a major biogeographic transition (i.e. Eurosiberian versus Mediterranean regions) in Western Europe. Our results show that the diversity patterns of bryophytes, lichens and vascular plants differ between contrasting coastal dynamics, regardless of the biogeographic context. Also, we found the absence of an explicit cross-taxa congruence among the diversity patterns of the three taxonomic groups. These results highlight the importance of taking into account the diversity of vascular plants, lichens and bryophytes, and the inclusion of other factors besides coastal dynamics, such as anthropogenic pressures. By doing so, a complementary view on the diversity patterns in secondary sand dunes can be provided to better guide conservation actions and monitoring strategies.
DeLTA: Automated cell segmentation, tracking, and lineage reconstruction using deep learning

Microscopy image analysis is a major bottleneck in quantification of single-cell microscopy data, typically requiring human supervision and curation, which limit both accuracy and throughput. To address this, we developed a deep learning-based image analysis pipeline that performs segmentation, tracking, and lineage reconstruction. Our analysis focuses on time-lapse movies of Escherichia coli cells trapped in a “mother machine” microfluidic device, a scalable platform for long-term single-cell analysis that is widely used in the field. While deep learning has been applied to cell segmentation problems before, our approach is fundamentally innovative in that it also uses machine learning to perform cell tracking and lineage reconstruction. With this framework we are able to get high fidelity results (1% error rate), without human supervision. Further, the algorithm is fast, with complete analysis of a typical frame containing ∼150 cells taking <700msec. The framework is not constrained to a particular experimental set up and has the potential to generalize to time-lapse images of other organisms or different experimental configurations. These advances open the door to a myriad of applications including real-time tracking of gene expression and high throughput analysis of strain libraries at single-cell resolution. Author Summary Automated microscopy experiments can generate massive data sets, allowing for detailed analysis of cell physiology and properties such as gene expression. In particular, dynamic measurements of gene expression with time-lapse microscopy have proved invaluable for understanding how gene regulatory networks operate. However, image analysis remains a key bottleneck in the analysis pipeline, typically requiring human supervision and a posteriori processing. Recently, machine learning-based approaches have ushered in a new era of rapid, unsupervised image analysis. In this work, we use and repurpose the U-Net deep learning algorithm to develop an image processing pipeline that can not only accurately identify the location of cells in an image, but also track them over time as they grow and divide. As an application, we focus on multi-hour time-lapse movies of bacteria growing in a microfluidic device. Our algorithm is accurate and fast, with error rates near 1% and requiring less than a second to analyze a typical movie frame. This increase in speed and fidelity has the potential to open new experimental avenues, e.g. where images are analyzed on-the-fly so that experimental conditions can be updated in real time.
Inclusion of kaolin in the feed of Japanese quails during the production phase

Background: Kaolin may improve quail performance by maintaining intestinal integrity and improving nutrient absorption. Objective: To evaluate the overall performance, egg quality, moisture, nitrogen and calcium content in the excreta, intestinal morphology and financial analysis of kaolin in Japanese quail feed during the production phase. Methods: A total of 192 Japanese quails, distributed in a completely randomized design with four treatments and six repetitions with eight birds each, were used. Kaolin levels added to the diet were 0, 1.5, 3.0, and 4.5%. Results: Kaolin reduced feed consumption. Additionally, egg production, feed conversion and viability increased. Moisture, nitrogen and calcium in the excreta decreased. Height and width of the intestinal villi increased with increasing levels of kaolin in the diet. Kaolin had no effect on egg quality. Inclusion level of 1.5% kaolin allowed for greater economic gains. Conclusion: Kaolin improved performance, intestinal morphology, and reduced the moisture, nitrogen and calcium contents in the excreta. Egg quality remained unchanged with the addition of kaolin, and the best economic response resulted with the addition 1.5% kaolin.
Learning from the environment: how predation changes the behavior of terrestrial Isopoda (Crustacea Oniscidea)

Terrestrial isopods have adapted to predatory pressures by evolving a variety of behaviors, which arise from a combination of specific traits, such as volvation and tonic immobility. Evolutionarily, these behavioral adaptations have been shown to increase the fitness of the individuals of the species who show them because the probability of being predated is reduced due to the loss of interest by the predator towards the immobile prey and the increase of interest towards the other mobile ones. Even if some of these behaviors have been shown to have a genetic basis, there is limited knowledge about the effects of environmental influences and predator-induced learning abilities on the antipredatory strategies of invertebrates, and isopods in particular. Our study aimed to understand the degree to which “nature” and “nurture” (i.e. environmental and genetic factors) and their interactions influence these antipredatory behaviors. There might be a difference in the behavior of wild and captive isopods in their volvation frequency and duration of tonic immobility due to environmental factors (i.e. predation) that induce learning-related behavioral changes. Therefore, we tested this hypothesis. We applied the three types of stimuli, which aim to simulate the interaction of the predator with the isopod. All three species showed a significant difference, between individuals collected in the field (wild) and raised in the laboratory (captive), in the reaction to the stimulus that simulates the fall from a bird’s beak or from the jaws of a lizard after a catch. Although volvation frequency was highly species- and stimulus-specific, the duration of tonic immobility and the delay in the response to each stimulus, when significant, was always higher in wild groups than captive ones. These substantial differences may reflect the evolutionary and ecological characteristics of each species and the importance of environmental pressures to shape the behavior of these invertebrates to optimize their life strategies.
Structure determination from lipidic cubic phase embedded microcrystals by MicroED

The lipidic cubic phase (LCP) technique has proved to facilitate the growth of high-quality crystals that are otherwise difficult to grow by other methods. Because crystals grown in LCP can be limited in size, improved techniques for structure determination from these small crystals are important. Microcrystal electron diffraction (MicroED) is a technique that uses a cryo-TEM to collect electron diffraction data and determine high-resolution structures from very thin micro and nanocrystals. In this work, we have used modified LCP and MicroED protocols to analyze crystals embedded in LCP. Proteinase K in LCP was used as a model system, and several LCP sample preparation strategies were tested. Among these, treatment with 2-Methyl-2,4-pentanediol (MPD) and lipase were both able to reduce the viscosity of the LCP and produce quality cryo-EM grids with well-diffracting crystals. These results set the stage for the use of MicroED to analyze other microcrystalline samples grown in LCP.
Nationwide comprehensive gastro-intestinal cancer cohorts

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. ARTICLE HISTORY Received 18 April 2017 Accepted 20 June 2017 CONTACT Hanneke W. M. van Laarhoven h.vanlaarhoven@amc.uva. nl Department of Medical Oncology, Academic Medical Center, Postbox 1100 DD, Amsterdam, The Netherlands These authors contributed equally to this article. These senior authors contributed equally to this article. Supplemental data for this article can be accessed here. 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/Licenses/by-nc-nd/ 4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. ACTA ONCOLOGICA, 2017 https://doi.org/10.1080/0284186X.2017. 1346381 D ow nl oa de d by [ T ilb ur g U ni ve rs ity ] at 0 4: 55 1 8 D ec em be r 20 17 Material and methods: All patients aged 18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.
Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome

CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signaling. Due to advances in next generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic syndrome (BCD) albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in thirteen participants presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described, and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome.
Dormancy dynamics and dispersal contribute to soil microbiome resilience

In disturbance ecology, stability is composed of resistance to change and resilience towards recovery after the disturbance subsides. Two key microbial mechanisms that can support microbiome stability include dormancy and dispersal. Specifically, microbial populations that are sensitive to disturbance can be re-seeded by local dormant pools of viable and reactivated cells, or by immigrants dispersed from regional metacommunities. However, it is difficult to quantify the contributions of these mechanisms to stability without, first, distinguishing the active from inactive membership, and, second, distinguishing the populations recovered by local resuscitation from those recovered by dispersed immigrants. Here, we investigate the contributions of dormancy dynamics (activation and inactivation), and dispersal to soil microbial community resistance and resilience. We designed a replicated, 45-week time-series experiment to quantify the responses of the active soil microbial community to a thermal press disturbance, including control mesocosms, disturbed mesocosms without dispersal, and disturbed mesocosms with dispersal after the release of the stressor. Communities were sensitive within one week of warming. Though the disturbed mesocosms did not fully recover within 29 weeks, resuscitation of thermotolerant taxa was key for community transition during the press, and both resuscitation of opportunistic taxa and immigration contributed to community resilience. Also, mesocosms with dispersal were more resilient than mesocosms without. This work advances the mechanistic understanding of how microbiomes respond to disturbances in their environment.
An in silico study of G protein-coupled-receptor activation, specifically in the corticotropin releasing factor receptor and the glucagon-like peptide receptor

iv List of Figures.ix List of Tables.xi Chapter 1: Introduction to Computational Drug Design.1 1.1 The Need for a Computational Approach.1 1.2 Methodologies.2 1.2. 1 Bioinformatics.2 1.2. 2 Homology Modeling.3 1.2. 3 Molecular Docking.3 1.2. 4 Molecular Dynamics Simulations.4 1.2. 5 MMGBSA Binding Energy Calculations.5 1.3 Thesis Outline.5 Chapter 2: Binding of Peptide Agonist Urocortin and Small Molecule Antagonist CP 376395 to the CRF1 Receptor Probed by Molecular Dynamics Simulations.8 2.
Distinct roles for innexin gap junctions and hemichannels in mechanosensation

Mechanosensation is central to a wide range of functions, including tactile and pain perception, hearing, proprioception, and control of blood pressure, but identifying the molecules underlying mechanotransduction has proved challenging. In Caenorhabditis elegans, the avoidance response to gentle body touch is mediated by 6 touch receptor neurons (TRNs), and is dependent on MEC-4, a DEG/ENaC channel. We show that hemichannels containing the innexin protein UNC-7 are also essential for gentle touch in the TRNs, as well as harsh touch in both the TRNs and the PVD nociceptors. UNC-7 and MEC-4 do not colocalize, suggesting that their roles in mechanosensory transduction are independent. Heterologous expression of unc-7 in touch-insensitive chemosensory neurons confers ectopic touch sensitivity, indicating a direct role for UNC-7 hemichannels in mechanosensation. The unc-7 touch defect can be rescued by the homologous mouse gene Panx1 gene, thus, innexin/pannexin proteins may play broadly conserved roles in neuronal mechanotransduction.
Interspecific interference competition between two field cricket species

Species interactions, such as interspecific competition, determine population dynamics and community structure. In a park of Amami Oshima Island, Japan, two field cricket species Teleogryllus occipitalis (Audinet‐Serville) (Gryllidae) and Loxoblemmus equestris Saussure (Gryllidae) are dominant species. We examined the interference competition at the nymph and adult stages in the two crickets under controlled laboratory conditions. Survival and emergence rates of T. occipitalis were not affected by the density of L. equestris, whereas survival and emergence rates of L. equestris decreased as the density of T. occipitalis increased. These results showed that T. occipitalis was competitively superior over L. equestris in species interactions. We discuss inconsistency between the results and coexistence of these two species under field conditions.
Conspecific olfactory preferences and interspecific divergence in odor cues in a chickadee hybrid zone

Abstract Understanding how mating cues promote reproductive isolation upon secondary contact is important in describing the speciation process in animals. Divergent chemical cues have been shown to act in reproductive isolation across many animal taxa. However, such cues have been overlooked in avian speciation, particularly in passerines, in favor of more traditional signals such as song and plumage. Here, we aim to test the potential for odor to act as a mate choice cue, and therefore contribute to premating reproductive isolation between the black‐capped (Poecile atricapillus) and Carolina chickadee (P. carolinensis) in eastern Pennsylvania hybrid zone populations. Using gas chromatography–mass spectrometry, we document significant species differences in uropygial gland oil chemistry, especially in the ratio of ester to nonester compounds. We also show significant preferences for conspecific over heterospecific odor cues in wild chickadees using a Y‐maze design. Our results suggest that odor may be an overlooked but important mating cue in these chickadees, potentially promoting premating reproductive isolation. We further discuss several promising avenues for future research in songbird olfactory communication and speciation.
Long-term impact of deficit irrigation on the physiology and growth of grapevine cv. ‘Prima’ grafted on various rootstocks

Testing the globally popular grapevine rootstocks for affinity with new grape cultivars or tolerance potential to stress factors like drought is essential for districts where supplemental irrigation is more frequently needed due to the pressures of a global climate change. In this study, a seasonal evaluation of leaf gas exchange, leaf temperature, leaf greenness (chlorophyll content prediction) and vegetative development of Vitis vinifera L. cv. ‘Prima’ grafted to different rootstock genotypes having great variability in drought tolerance, were investigated. The experiment was conducted in a controlled experimental glasshouse on two-year-old soilless grown ‘Prima’ vines grafted on nine rootstocks [44-53 M, 5 BB, 140 Ru, Ramsey (Syn. Salt Creek), 99 R, Saint George (Syn. Rupestris du Lot), 41 B, 1613 C and 420 A]. A long-term deficit irrigation (DI) was imposed before bud break by reducing water supply to 40% of field capacity derived from concurrent measurements of water content of growth medium and maintained until the end of vegetation period. The rootstocks significantly modulated the physiology and vegetative growth of the scion cultivar in varying degrees according to their genetic features. Among them, 140 Ru rootstock found to be more prominent in terms of mitigating the adverse effect of water deficit on physiology and growth of the scion genotype ‘Prima’ as there were no significant difference between deficit and full irrigation treatments for most of parameters investigated. In general, the ‘Prima’ scion performed better when the rootstocks coming from V. berlandieri × V. rupestris pedigree rather than the others including V. berlendieri × V. riparia.