Miracle-dz/UniFAR-FTUs huggingface dataset:
The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK

The alarmin S100A8/A9 is implicated in sterile inflammation‐induced bone resorption and has been shown to increase the bone‐resorptive capacity of mature osteoclasts. Here, we investigated the effects of S100A9 on osteoclast differentiation from human CD14+ circulating precursors. Hereto, human CD14+ monocytes were isolated and differentiated toward osteoclasts with M‐CSF and receptor activator of NF‐κB (RANK) ligand (RANKL) in the presence or absence of S100A9. Tartrate‐resistant acid phosphatase staining showed that exposure to S100A9 during monocyte‐to‐osteoclast differentiation strongly decreased the numbers of multinucleated osteoclasts. This was underlined by a decreased resorption of a hydroxyapatite‐like coating. The thus differentiated cells showed a high mRNA and protein production of proinflammatory factors after 16 h of exposure. In contrast, at d 4, the cells showed a decreased production of the osteoclast‐promoting protein TNF‐α. Interestingly, S100A9 exposure during the first 16 h of culture only was sufficient to reduce osteoclastogenesis. Using fluorescently labeled RANKL, we showed that, within this time frame, S100A9 inhibited the M‐CSF‐mediated induction of RANK. Chromatin immunoprecipitation showed that this was associated with changes in various histone marks at the epigenetic level. This S100A9‐induced reduction in RANK was in part recovered by blocking TNF‐α but not IL‐1. Together, our data show that S100A9 impedes monocyte‐to‐osteoclast differentiation, probably via a reduction in RANK expression. —Di Ceglie, I. , Blom, A. B. , Davar, R. , Logie, C. , Martens, J. H. A. , Habibi, E. , Böttcher, L. ‐M. , Roth, J., Vogl, T. , Goodyear, C. S. , van der Kraan, P. M. , van Lent, P. L. , van den Bosch, M. H. The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK. FASEB J. 33, 10104–10115 (2019). www.fasebj. org
A COMPREHENSIVE STUDY ON ONE-WAY BACKSCATTER TRAFFIC ANALYSIS

vii List of Abbreviations and Symbols Used . viii Acknowledgements . x Chapter
A Financial Condition Index for India through Incorporation of Commercial Bank and Other Lending

The aim of this paper is to construct a Financial Condition Index (FCI) in context of Indian economy by incorporating a financial variables, namely commercial bank and other lending with two monetary variables, real exchange rate and short term interest rate. The paper explores if this index could act as an indicator of fluctuations in the real economy. The FCI is constructed following a weighted-sum method, with weights been assigned on the basis of estimated relative impact of each of the variables on the Gross Domestic Product (GDP) of India. The correlation between FCI thus constructed, and the inflation rate in the economy for two decades is found to be rather weak; highlighting the possibility that the dynamics of borrowing and the aggregate demand side of the Indian economy is rather unique.
Effect of Slip Condition on Couple Stress Fluid Flow in a Channel with Mild Stenosis in the Presence of Uniform Magnetic Field

The steady flow of an incompressible couple stress fluid in a two dimensional uniform channel with stenosis under the influence of a magnetic field has been investigated. Assuming the stenosis to be mild, the flow equations have been analytically solved using the slip condition and expressions for the resistance to flow and wall shear stress have been derived. The effects of various parameters on these flow variables have been studied. It is found that the resistance to flow as well as the wall shear stress increase with the height of the stenosis and decrease with the couple stress and magnetic parameters. The effects of other parameters on resistance to flow and the wall shear stress have been considered.
The economic impact of the invasion of Acacia saligna in Israel

This paper illustrates the use of alternative, non-market valuation methods to estimate the economic value of ecological damage caused by the invasive plant Acacia saligna. We discuss the motivation to perform an economic valuation for bio-invasion in general and then examine the costs and benefits of conservation management programmes that reduce the risk of A. saligna invasion at the Nizzanim Long-Term Ecosystem Research (LTER) nature reserve in Israel. The study found that the annual mean willingness to pay (WTP) for containment or eradication of A. saligna was US$8.41 and US$8.83, respectively. The value placed on conserving the nature reserve was then compared to the cost of containment or eradication of the species, enabling a standard economic benefit–cost analysis. The result of this analysis showed that, using the most conservative method of valuation of the nature reserve, eradication of A. saligna gave a net benefit.
Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency

Sodium taurocholate cotransporting polypeptide (NTCP, encoded by Slc10a1/SLC10A1) deficiency can result in hypercholanemia but no obvious symptoms in both mice and humans. However, the consequence of and response to long-term hypercholanemia caused by NTCP deficiency remain largely unexplored. Here, we analyzed lifelong dynamics of serum total bile acid (TBA) levels in Slc10a1−/− mice, and we also assessed changes of TBA levels in 33 young individuals with SLC10A1 loss-of-function variant p.Ser267Phe. We found that overall serum TBA levels tended to decrease gradually with age in both Slc10a1−/− mice and p.Ser267Phe individuals. Liver mRNA profiling revealed notable transcription alterations in hypercholanemic Slc10a1−/− mice, including inhibition of bile acid (BA) synthesis, enhancement of BA detoxification, and altered BA transport. Members of the sulfotransferase (SULT) family showed the most dramatic increases in livers of hypercholanemic Slc10a1−/− mice, and one of their BA sulfates, taurolithocholic acid 3-sulfate, significantly increased. Importantly, consistent with the mouse studies, comprehensive profiling of 58 BA species in sera of p.Ser267Phe individuals revealed a markedly increased level of BA sulfates. Together, our findings indicate that the enhanced BA sulfation is a major mechanism for BA detoxification and elimination in both mice and humans with Slc10a1/SLC10A1 deficiency.
Circulating MACC1 Transcripts in Glioblastoma Patients Predict Prognosis and Treatment Response

Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacks reliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associated in colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinical outcome and therapy response in glioblastomas. MACC1 transcripts were significantly higher in patients compared to controls. Low MACC1 levels clustered together with other prognostically favorable markers. It was associated with patients’ prognosis in conjunction with the isocitrate dehydrogenase (IDH) mutation status: IDH1 R132H mutation and low MACC1 was most favorable (median overall survival (OS) not yet reached), IDH1 wildtype and high MACC1 was worst (median OS 8.1 months), while IDH1 wildtype and low MACC1 was intermediate (median OS 9.1 months). No patients displayed IDH1 R132H mutation and high MACC1. Patients with low MACC1 levels receiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1 levels (median OS 8.1 months). Patients not receiving the standard regimen showed the worst prognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulating MACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcome prediction and help define more precise risk categories of glioblastoma patients.
New Spirinia and Stygodesmodora species (Nematoda, Spiriniinae) from the Southwest Pacific, and a revision of the related genera Spirinia, Chromaspirina and Perspiria

Two new species of the family Desmodoridae are described from the upper continental slope of New Zealand, Southwest Pacific, and the genera Spirinia , Chromaspirina and Perspiria are revised. Spirinia verecunda sp. nov. is characterised by a short, stout body, cuticle covered in minute, hair-like structures, unispiral amphideal aperture and cryptospiral amphideal fovea, buccal cavity with small dorsal tooth and minute subventral teeth, eight oblong glands surrounding anterior portion of pharynx, large sperm cells, spicules with weak capitulum, and the absence of precloacal supplements. Stygodesmodora confusa sp. nov. is characterised by a relatively short body, spiral amphids with 1.2–1.4 turns, cephalic setae situated at or slightly posterior to mid-level of amphid, and males with four precloacal supplements consisting of short setae on wide bases. Like other species of the genus, S. confusa sp. nov. is characterised by an annulated head region, but in some specimens the cuticle annulations are restricted to the dorsal and ventral sides of the head. S. confusa sp. nov. shows similarities with species of other desmodorid genera (i.e., Echinodesmodora , Bolbonema ), but can be differentiated from them by the presence of an annulated head region and amphideal plates. The genera Spirinia, Chromaspirina and Perspiria have very similar morphologies and differ mainly in the size and structure of the buccal cavity ( Spirinia vs Chromaspirina ) or the shape of the tail and placement of the amphids relative to the cuticle annulations ( Spirinia vs Perspiria ); their diagnoses are clarified and some nomenclatural changes are proposed to eliminate overlap in the definitions of these genera.
Executive Functioning and Narrative Language in Children With Dyslexia.

Purpose Children with dyslexia often struggle with nonphonological aspects of language and executive functioning. The purpose of this study was to investigate the impact of executive functioning on language abilities at both structural (e.g., grammar in sentences) and functional (e.g., narrative) levels in 92 third- and 4th-grade students with dyslexia. Additionally, we asked if working memory updating contributed a significant amount of variance in narrative language ability beyond what would be expected by students' structural language skills alone. Method Students' language and executive functioning skills were evaluated using a range of language and cognitive measures including the Clinical Evaluation of Language Fundamentals-Fourth Edition ( Semel, Wiig, & Secord, 2003 ), the Peabody Picture Vocabulary Test-Fourth Edition ( Dunn & Dunn, 2007 ), the Test of Narrative Language ( Gillam & Pearson, 2004 ), the Delis-Kaplan Executive Function Scale ( Kaplan, Kramer, & Delis, 2001 ), and the Corsi Block-Tapping Test (WISC-IV Integrated; Kaplan, Fein, Kramer, Delis, & Morris, 2004 ). Results Low correlations between the language measures suggested that each of these assessments captures a unique element of language ability for children with dyslexia. Hierarchical regression analysis indicated that working memory updating accounted for a significant amount of unique variance in oral narrative production beyond what would be expected by structural language ability. Conclusions The range of performance found across language measures suggests that it may be important to include a variety of language measures assessing both structural and functional language skills when evaluating children with dyslexia. Including cognitive measures of executive functioning may also be key to determine if deficits in working memory updating are contributing to functional expressive language difficulties.
SPIDER model simulations of aircraft plume dilution

To include the effect of aircraft plume processes (effective emissions indices) in large scale chemistry transport models and climate-chemistry models, the instantaneous dispersion (ID) and single-plume (SD) approaches exist. We use the box model SPIDER to evaluate these two con- cepts. Its simplified NOx-O3 chemistry parameterises only the most relevant non-linear processes. SPIDER simulations for varying NOx background reveal the largest difference between ID and SP approaches in clean-air conditions. For a NOx background of ~0.2 nmol mol -1 , the ID and SP ap- proaches result in aviation-induced O3 changes of opposite signs. Hence, this transition regime may require more attention in plume parameterisations applied in global atmospheric models.
Dynamic Mitochondrial Migratory Features Associated with Calcium Responses during T Cell Antigen Recognition

Key Points Microfluidics provides precision for manipulating cell–cell interactions. Complex mitochondrial movement occurs during initial T cell:APC synapse formation. Mitochondrial positioning is a strong predictor of calcium response. A T cell clone is able to distinguish Ags in the form of peptide–MHC complexes with high specificity and sensitivity; however, how subtle differences in peptide–MHC structures translate to distinct T cell effector functions remains unknown. We hypothesized that mitochondrial positioning and associated calcium responses play an important role in T cell Ag recognition. We engineered a microfluidic system to precisely manipulate and synchronize a large number of cell–cell pairing events, which provided simultaneous real-time signaling imaging and organelle tracking with temporal precision. In addition, we developed image-derived metrics to quantify calcium response and mitochondria movement. Using myelin proteolipid altered peptide ligands and a hybridoma T cell line derived from a mouse model of experimental autoimmune encephalomyelitis, we observed that Ag potency modulates calcium response at the single-cell level. We further developed a partial least squares regression model, which highlighted mitochondrial positioning as a strong predictor of calcium response. The model revealed T cell mitochondria sharply alter direction within minutes following exposure to agonist peptide Ag, changing from accumulation at the immunological synapse to retrograde movement toward the distal end of the T cell body. By quantifying mitochondria movement as a highly dynamic process with rapidly changing phases, our result reconciles conflicting prior reports of mitochondria positioning during T cell Ag recognition. We envision applying this pipeline of methodology to study cell interactions between other immune cell types to reveal important signaling phenomenon that is inaccessible because of data-limited experimental design.
FRET-based sensor for CaMKII activity (FRESCA): A useful tool for assessing CaMKII activity in response to Ca2+ oscillations in live cells

Ca2+ oscillations and consequent Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation are required for embryogenesis, as well as neuronal, immunological, and cardiac signaling. Fertilization directly results in Ca2+ oscillations, but the resultant pattern of CaMKII activity remains largely unclear. To address this gap, we first employed the one existing biosensor for CaMKII activation. This sensor, Camui, comprises CaMKIIα and therefore solely reports on the activation of this CaMKII variant. Additionally, to detect the activity of all endogenous CaMKII variants simultaneously, we constructed a substrate-based sensor for CaMKII activity, FRESCA (FRET-based sensor for CaMKII activity). To examine the differential responses of the Camui and FRESCA sensors, we used several approaches to stimulate Ca2+ release in mouse eggs, including addition of phospholipase Cζ cRNA, which mimics natural fertilization. We found that the Camui response is delayed or terminates earlier than the FRESCA response. FRESCA enables assessment of endogenous CaMKII activity in real-time by both fertilization and artificial reagents, such as Sr2+, which also leads to CaMKII activation. FRESCA's broad utility will be important for optimizing artificial CaMKII activation for clinical use to manage infertility. Moreover, FRESCA provides a new view on CaMKII activity, and its application in additional biological systems may reveal new signaling paradigms in eggs, as well as in neurons, cardiomyocytes, immune cells, and other CaMKII-expressing cells.
Impact of the Quebec Alzheimer Plan on the detection and management of Alzheimer disease and other neurocognitive disorders in primary health care: a retrospective study.

BACKGROUND The Quebec Alzheimer Plan aims to improve care provided to patients with neurocognitive disorders in Family Medicine Groups (FMGs) (multidisciplinary team-based primary care practices). The objective of this study was to determine changes in the detection and management of neurocognitive disorders following implementation of the plan, in 2014. METHODS This was a retrospective chart review before and after implementation of the Quebec Alzheimer Plan in 13 FMGs. We reviewed 1919 randomly selected charts of patients aged 75 years or more and 945 randomly selected charts of patients in this age group with neurocognitive disorders. In the first group, selected outcomes were proportion of patients with documentation of cognitive status, documented diagnosis of neurocognitive disorder, documented cognitive testing and referral to a memory clinic. In patients with neurocognitive disorders, the outcomes were number of contacts with an FMG, quality of follow-up score (documented assessments in 10 domains: cognitive testing, functional status, behavioural and psychological symptoms of dementia, weight, caregiver needs, driving status, home care needs, community service needs, absence of anticholinergic medication and management of dementia medications) and proportion referred to a memory clinic. RESULTS Significantly more patients aged 75 or more had documentation of cognitive status in their chart after plan implementation than before implementation (440 [45.1%] v. 351 [37.2%]) (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.18-1.81). No significant changes were found in documented diagnosis of neurocognitive disorders, cognitive testing or referral to a memory clinic. Among patients with neurocognitive disorders, the number of contacts with an FMG (adjusted mean difference 1.6, 95% CI 0.3-2.8) and quality of follow-up score (adjusted mean difference 6.6, 95% CI 3.9-9.2) increased significantly, without significant changes in the number of referrals to a memory clinic. INTERPRETATION The results suggest that the Quebec Alzheimer Plan is feasible and beneficial in terms of detection and management of neurocognitive disorders, without an increase in referral to specialists. The findings will be used to scale up the Quebec Alzheimer Plan and to develop the Canadian federal dementia strategy.
Development of novel microsatellite markers for a specialist species of Lepidoptera, Boloria aquilonaris (Nymphalidae), based on 454 sequences

Microsatellites are the most common markers used in population and conservation genetic studies. However, their isola- tion is laborious and expensive. In some taxa, such as Lepidoptera, it is particularly difficult to isolate microsatellite markers due to the high similarity of the flanking regions of different loci and the presence of null alleles. Here we isolated microsatellites of the endangered butterfly Boloria aquilonaris using 454 GS-FLX Titanium pyro-sequences of biotin enriched DNA libraries and tested the success of cross-amplification on the sister-species B. eunomia. Fifteen polymorphic microsatellite loci were isolated in B. aquilonaris using initially 101 stringently designed primer pairs. Unlike in many other studies of microsatellite isolation in Lepidoptera, few null alleles were detected and only at very low frequencies. Additionally, the raw data set can still be used for the isolation of other microsatellite loci. None of the selected polymorphic loci for B. aquilonaris gave clear banding patterns for B. eunomia, although about 15 other loci gave promising banding patterns for the latter species. Low intra- and inter-specific transferability of developed markers in this study also lends support to the hypothesis that the evolution of the genome of Lepidoptera is dissimilar from that of other organisms.
Tectonic evolution of the Northeastern South China Sea from seismic interpretation

[1] We interpret a grid of 2-D seismic reflection profiles to resolve the tectonic evolution of the northeastern South China Sea (SCS), identifying two significant postbreakup events, T1 and T2, which occurred before the end of the SCS opening. In the absence of the drilling data in the deep basin, we date these two events using the identification of the magnetic anomalies, the age of major unconformities at Ocean Drilling Program Site 1148 drilled on the northeastern SCS margin, and the age of basalt samples in the deep SCS. The tectonic phase T1 is a slight tensional tectonic event which occurred in the deep SCS, south of the Luzon-Ryukyu Transform Plate Boundary (LRTPB). It is characterized by oceanic tilted blocks and fan-shaped deposits, which developed 8–10 Myr after the onset of SCS seafloor spreading (37.8 Ma). It corresponds to the first ENE–WSW to E–W change in spreading direction, which occurred around chron C10 (∼28.7 Ma). Event T2 is a magmatic phase observed in the deep SCS, south of the LRTPB. It is characterized by the uplift of former spreading features caused by an early Miocene (∼22 Ma) magmatic phase, which is also recorded in north and south-central Taiwan.
Mitochondrial Transcriptome Control and Intercompartment Cross-Talk During Plant Development

We address here organellar genetic regulation and intercompartment genome coordination. We developed earlier a strategy relying on a tRNA-like shuttle to mediate import of nuclear transgene-encoded custom RNAs into mitochondria in plants. In the present work, we used this strategy to drive trans-cleaving hammerhead ribozymes into the organelles, to knock down specific mitochondrial RNAs and analyze the regulatory impact. In a similar approach, the tRNA mimic was used to import into mitochondria in Arabidopsis thaliana the orf77, an RNA associated with cytoplasmic male sterility in maize and possessing sequence identities with the atp9 mitochondrial RNA. In both cases, inducible expression of the transgenes allowed to characterise early regulation and signaling responses triggered by these respective manipulations of the organellar transcriptome. The results imply that the mitochondrial transcriptome is tightly controlled by a “buffering” mechanism at the early and intermediate stages of plant development, a control that is released at later stages. On the other hand, high throughput analyses showed that knocking down a specific mitochondrial mRNA triggered a retrograde signaling and an anterograde nuclear transcriptome response involving a series of transcription factor genes and small RNAs. Our results strongly support transcriptome coordination mechanisms within the organelles and between the organelles and the nucleus.