Miracle-dz/UniFAR-FTUs huggingface dataset:
Infratentorial and spinal cord lesions: Cumulative predictors of long-term disability?

Objective: The objective of the study was to determine whether early infratentorial and/or spinal cord lesions are long-term cumulative predictors of disability progression in multiple sclerosis (MS). Methods: We selected 153 MS patients from the longitudinal Amsterdam MS cohort. Lesion analysis was performed at baseline and year 2. Disability progression after 6 and 11 years was measured using the Expanded Disability Status Scale (EDSS) and EDSS-plus (including 25-foot walk and 9-hole peg test). Patients with spinal cord or infratentorial lesions were compared for the risk of 6- and 11-year disability progression to patients without spinal cord or infratentorial lesions, respectively. Subsequently, patients with lesions on both locations were compared to patients with only spinal cord or only infratentorial lesions. Results: Baseline spinal cord lesions show a higher risk of 6-year EDSS progression (odds ratio (OR): 3.6, p = 0.007) and EDSS-plus progression (OR: 2.5, p = 0.028) and 11-year EDSS progression (OR: 2.8, p = 0.047). Patients with both infratentorial and spinal cord lesions did not have a higher risk of 6-year disability progression than patients with only infratentorial or only spinal cord lesions. Conclusion: The presence of early spinal cord lesions seems to be a dominant risk factor of disability progression. Simultaneous presence of early infratentorial and spinal cord lesions did not undisputedly predict disability progression.
Analysis of lipoprotein transport depletion in Vibrio cholerae using CRISPRi

Significance In this study, we interrogated the role of Vibrio cholerae essential genes in viability and virulence using CRISPR-interference (CRISPRi) and found that depletion of the essential lipoprotein transport pathway causes extrusion of large membrane vesicles and ultimately leads to this pathogen’s death. Our work generates mechanistic insights into fundamental areas of V. cholerae biology, with important implications for medical prevention of devastating cholera outbreaks. Genes necessary for the survival or reproduction of a cell are an attractive class of antibiotic targets. Studying essential genes by classical genetics, however, is inherently problematic because it is impossible to knock them out. Here, we screened a set of predicted essential genes for growth inhibition using CRISPR-interference (CRISPRi) knockdown in the human pathogen Vibrio cholerae. We demonstrate that CRISPRi knockdown of 37 predicted essential genes inhibits V. cholerae viability, thus validating the products of these genes as potential drug target candidates. V. cholerae was particularly vulnerable to lethal inhibition of the system for lipoprotein transport (Lol), a central hub for directing lipoproteins from the inner to the outer membrane (OM), with many of these lipoproteins coordinating their own essential processes. Lol depletion makes cells prone to plasmolysis and elaborate membrane reorganization, during which the periplasm extrudes into a mega outer membrane vesicle or “MOMV” encased by OM which dynamically emerges specifically at plasmolysis sites. Our work identifies the Lol system as an ideal drug target, whose inhibition could deplete gram-negative bacteria of numerous proteins that reside in the periplasm.
Memory hierarchy characterization of SPEC CPU2006 and SPEC CPU2017 on the Intel Xeon Skylake-SP

SPEC CPU is one of the most common benchmark suites used in computer architecture research. CPU2017 has recently been released to replace CPU2006. In this paper we present a detailed evaluation of the memory hierarchy performance for both the CPU2006 and single-threaded CPU2017 benchmarks. The experiments were executed on an Intel Xeon Skylake-SP, which is the first Intel processor to implement a mostly non-inclusive last-level cache (LLC). We present a classification of the benchmarks according to their memory pressure and analyze the performance impact of different LLC sizes. We also test all the hardware prefetchers showing they improve performance in most of the benchmarks. After comprehensive experimentation, we can highlight the following conclusions: i) almost half of SPEC CPU benchmarks have very low miss ratios in the second and third level caches, even with small LLC sizes and without hardware prefetching, ii) overall, the SPEC CPU2017 benchmarks demand even less memory hierarchy resources than the SPEC CPU2006 ones, iii) hardware prefetching is very effective in reducing LLC misses for most benchmarks, even with the smallest LLC size, and iv) from the memory hierarchy standpoint the methodologies commonly used to select benchmarks or simulation points do not guarantee representative workloads.
A role for S-nitrosylation of the SUMO-conjugating enzyme SCE1 in plant immunity

Significance S-nitrosylation, the addition of a nitric oxide (NO) moiety to a reactive protein cysteine (Cys) thiol to form an S-nitrosothiol (SNO), is emerging as a pivotal redox-based, posttranslational modification (PTM) during plant immune function. However, the Cys target sites of NO bioactivity and the associated consequences on cellular signaling are not well defined. Our findings suggest that S-nitrosylation of small ubiquitin-like modifier (SUMO)-conjugating enzyme 1 (SCE1) at Cys139 controls SUMOylation, a protein-based PTM that negatively regulates plant immunity through conjugation of SUMO1/2. This Cys is evolutionary conserved and specifically S-nitrosylated in the human homolog, UBC9, implying that this mechanism might be conserved across phylogenetic kingdoms. SUMOylation, the covalent attachment of the small ubiquitin-like modifier (SUMO) to target proteins, is emerging as a key modulator of eukaryotic immune function. In plants, a SUMO1/2-dependent process has been proposed to control the deployment of host defense responses. The molecular mechanism underpinning this activity remains to be determined, however. Here we show that increasing nitric oxide levels following pathogen recognition promote S-nitrosylation of the Arabidopsis SUMO E2 enzyme, SCE1, at Cys139. The SUMO-conjugating activities of both SCE1 and its human homolog, UBC9, were inhibited following this modification. Accordingly, mutation of Cys139 resulted in increased levels of SUMO1/2 conjugates, disabled immune responses, and enhanced pathogen susceptibility. Our findings imply that S-nitrosylation of SCE1 at Cys139 enables NO bioactivity to drive immune activation by relieving SUMO1/2-mediated suppression. The control of global SUMOylation is thought to occur predominantly at the level of each substrate via complex local machineries. Our findings uncover a parallel and complementary mechanism by suggesting that total SUMO conjugation may also be regulated directly by SNO formation at SCE1 Cys139. This Cys is evolutionary conserved and specifically S-nitrosylated in UBC9, implying that this immune-related regulatory process might be conserved across phylogenetic kingdoms.
Tannin-containing legumes and forage diversity influence foraging behavior, diet digestibility and nitrogen excretion by lambs.

Diverse combinations of forages with different nutrient profiles and plant secondary compounds may improve intake and nutrient utilization by ruminants. We tested the influence of diverse dietary combinations of tannin- (sainfoin-Onobrichis viciifolia; birdsfoot trefoil-Lotus corniculatus) and non-tannin- (alfalfa-Medicago sativa L.) containing legumes on intake and diet digestibility in lambs. Freshly-cut birdsfoot trefoil, alfalfa and sainfoin were offered in ad libitum amounts to 42 lambs in individual pens assigned to 7 treatments (6 animals/treatment): (i) single forage species [sainfoin (SF), birdsfoot trefoil (BFT) and alfalfa (ALF)], (ii) all possible 2-way choices of the three forage species [alfalfa-sainfoin (ALF-SF), alfalfa-birdsfoot trefoil (ALF-BFT) and sainfoin-birdsfoot trefoil (SF-BFT)], or (iii) a choice of all three forages [alfalfa-sainfoin-birdsfoot trefoil (ALF-SF-BFT)]. Dry matter intake (DMI) was greater in ALF than in BFT (P=0.002), and DMI in SF tended to be greater than in BFT (P=0.053). However, when alfalfa was offered in a choice with either of the tannin-containing legumes (ALF-SF; ALF-BFT), DMI did not differ from ALF, whereas DMI in SF-BFT did not differ from SF (P>0.10). When lambs were allowed to choose between two or three legume species, DMI was greater (36.6 vs 33.2 g/kg BW; P=0.038) or tended to be greater (37.4 vs 33.2 g/kg BW; P=0.067) than when lambs were fed single species respectively. Intake did not differ between two- or three-way choice treatments (P=0.723). Lambs preferred alfalfa over the tannin-containing legumes in a 70:30 ratio for 2-way choices, and alfalfa>sainfoin>birdsfoot trefoil in a 53:33:14 ratio for the 3-way choice. In vivo digestibility (DMD) was SF > BFT (72.0 vs 67.7%; P=0.012) and DMD in BFT tended to be greater than in ALF (64.6%; P=0.061). Nevertheless, when alfalfa was offered in a choice with either sainfoin or birdsfoot trefoil (ALF-SF; ALF-BFT), DMD was greater than ALF (P<0.001 and P=0.007, respectively) suggesting positive associative effects. The SF treatment had lower blood urea nitrogen and greater fecal N/N Intake ratios than the ALF, BFT or ALF-BFT treatments (P<0.05), implying a shift in the site of N excretion from urine to feces. In conclusion, offering diverse combinations of legumes to sheep enhanced intake and diet digestibility relative to feeding single species, while allowing for the incorporation of beneficial bioactive compounds like condensed tannins into the diet.
Antibacterial Activity of Ag‐Hydroxyapatite Coating Against Hematogenous Infection by Methicillin‐Resistant Staphylococcus aureus in the Rat Femur

Several antibacterial materials have been developed to prevent periprosthetic joint infection and thus prevent serious complications for patients and surgeons. However, no study has addressed the activity of antibacterial materials against hematogenous infection. The present study evaluated the antibacterial activity of a silver‐containing hydroxyapatite‐coated implant against methicillin‐resistant Staphylococcus aureus (MRSA) hematogenous infection. Implants coated with hydroxyapatite and silver‐hydroxyapatite were inserted into rats’ right and left femurs, respectively, after which the animals were infected with S. aureus via a tail vessel. About 107 colony‐forming units was the optimal bacterial number for the establishment of S. aureus hematogenous infection. Bacterial loads and C‐reactive protein in the blood were measured to confirm bacteremia and inflammation. Fourteen days after the infection, bacterial loads were statistically lower in the femurs containing silver‐hydroxyapatite‐coated implants than in those with hydroxyapatite‐coated implants (p = 0.022). Thus, silver‐hydroxyapatite‐coated implants might provide antibacterial activity against MRSA hematogenous infection in the postoperative period. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2655–2660, 2019
Examining Depression Among Perpetrators of Intimate Partner Homicide

Male depression has been recognized as an important factor in some cases of intimate partner violence but there is a paucity of literature connecting depression and intimate partner homicide (IPH). This retrospective study provides a preliminary analysis that distinguished depressed from nondepressed perpetrators of IPH from a sample of 135 cases analyzed by a coroner’s homicide death review committee in Ontario, Canada. Depressed perpetrators were more likely to commit homicide-suicide and had almost 1.5 times the number of risk factors present than nondepressed perpetrators. Consistent with the existing literature, the results indicated that depressed perpetrators were significantly older, more likely to commit homicide-suicide than homicide only, more likely to have prior threats or attempts of suicide, more likely to have been abused or witnessed domestic violence as a child than nondepressed perpetrators and more likely to exhibit sexual jealousy. The implications for these findings are outlined in terms of training of mental health professionals and public awareness about the potential lethality of domestic violence.
Beliefs and challenges held by medical staff about providing emergency care to migrants: an international systematic review and translation of findings to the UK context

Objective Migration has increased globally. Emergency departments (EDs) may be the first and only contact some migrants have with healthcare. Emergency care providers’ (ECPs) views concerning migrant patients were examined to identify potential health disparities and enable recommendations for ED policy and practice. Design Systematic review and meta-synthesis of published findings from qualitative studies. Data sources Electronic databases (Ovid Medline, Embase (via Ovid), PsycINFO (via OVID), CINAHL, Web of Science and PubMed), specialist websites and journals were searched. Eligibility criteria Studies employing qualitative methods published in English. Settings EDs in high-income countries. Participants ECPs included doctors, nurses and paramedics. Topic of enquiry Staff views on migrant care in ED settings. Data extraction and synthesis Data that fit the overarching themes of ‘beliefs’ and ‘challenges’ were extracted and coded into an evolving framework. Lines of argument were drawn from the main themes identified in order to infer implications for UK policy and practice. Results Eleven qualitative studies from Europe and the USA were included. Three analytical themes were found: challenges in cultural competence; weak system organisation that did not sufficiently support emergency care delivery; and ethical dilemmas over decisions on the rationing of healthcare and reporting of undocumented migrants. Conclusion ECPs made cultural and organisational adjustments for migrant patients, however, willingness was dependent on the individual’s clinical autonomy. ECPs did not allow legal status to obstruct delivery of emergency care to migrant patients. Reported decisions to inform the authorities were mixed; potentially leading to uncertainty of outcome for undocumented migrants and deterring those in need of healthcare from seeking treatment. If a charging policy for emergency care in the UK was introduced, it is possible that ECPs would resist this through fears of widening healthcare disparities. Further recommendations for service delivery involve training and organisational support.
Changing the biological Rosetta stone: the (commercial) potential of recoded microbes

In 1822, the French Egyptologist Jean-Franc ois Champollion announced the deciphering of the Rosetta stone, the key for translating Egyptian hieroglyphs, thereby enabling an unprecedented insight into ancient Egypt history. Life has its own Rosetta stone, the genetic code, decoded by Marshall Nirenberg in 1960s. While the genetic code is universal (albeit exceptions) and has not undergone major changes since the last universal common ancestor, technological progress allows synthetic biologists to increasingly re-write the biological Rosetta.
A Dissipative Particle Dynamics Study of Flow Behaviors in Ultra High Molecular Weight Polyethylene/Polyamide 6 Blends Based on Souza-Martins Method

This paper presents our study on the use of dissipative particle dynamics (DPD) simulations to discover the flow behavior in ultra high molecular weight polyethylene/polyamide 6 (UHMWPE/PA6) blends associated with extensional-shear coupled flow, based on the Souza-Martins method, for the first time. By way of simulations, we aimed at investigating the mesoscopic morphology and alignment behavior in response to extensional-shear coupled flow, in comparison with simple shear flow and simple extensional flow. Our results reveal that the aggregation of polymers is noticeable under zero flow, as expected. Within the considered range of extensional-shear coupled rates, the morphology transforms from micelle-like clusters to a chain-like network structure by increasing coupled rates from 0.01 to 2.0. Furthermore, it shows a linear distribution along the flow direction at a high coupled rate. It can be concluded that the flow behaviors in UHMWPE/PA6 blends are significantly impacted by extensional-shear coupled rates. The orientation behavior induced by extensional-shear coupled flow is more obvious than shear flow, even though flow variations and mass fractions yield less effects on the distribution behaviors of UHMWPE/PA6 blends. The DPD results are verified by mean square displacement (MSD) as a function of simulation time and relative concentration distribution along Z direction.
Oxidative damage to membrane lipids in the thyroid – no differences between sexes

Abstract It has long been observed that thyroid diseases are more prevalent in women than in men. However, there are limited experimental data demonstrating mechanisms by which sex differences in thyroid diseases may occur and exact molecular mechanisms involved are still far from clear. The aim of the study was to evaluate if there are sex differences concerning oxidative damage to membrane lipids in thyroid homogenates in response to Fenton reaction substrates, i.e., Fe2+ and/or H2O2, and, additionally, in response to potentially protective agent, i.e., melatonin. Homogenates of male or female thyroids collected from adult swine (Sus scrofa domesticus) at slaughter were incubated in the presence of H2O2 and/or Fe2+ without or with addition of melatonin. Malondialdehyde + 4-hydroxyalkenals concentration (LPO index) was measured spectrophotometrically. Neither H2O2 nor Fe2+, when used separately, did affect the level of lipid peroxidation in both male and female porcine thyroid homogenates. When H2O2 (0.5 mM) was used together with different concentrations of Fe2+, the level of lipid peroxidation increased significantly in both male and female porcine thyroid homogenates, with clear Fe2+ concentration-dependent stimulatory effect, but without differences between sexes. No sex-specific differences was found concerning oxidative damage to membrane lipids in porcine thyroid in response to Fenton reaction substrates and/or to melatonin. The lack of expected differences may be due to potentially lower sensitivity of membrane lipids comparing to other biological macromolecules to pro-/antioxidative agents in the thyroid. However, further studies should be performed to explain the discussed issue.
Interpreting in vivo calcium signals from neuronal cell bodies, axons, and dendrites: a review

Abstract. Calcium imaging is emerging as a popular technique in neuroscience. A major reason is that intracellular calcium transients are reflections of electrical events in neurons. For example, calcium influx in the soma and axonal boutons accompanies spiking activity, whereas elevations in dendrites and dendritic spines are associated with synaptic inputs and local regenerative events. However, calcium transients have complex spatiotemporal dynamics, and since most optical methods visualize only one of the somatic, axonal, and dendritic compartments, a straightforward inference of the underlying electrical event is typically challenging. We highlight experiments that have directly calibrated in vivo calcium signals recorded using fluorescent indicators against electrophysiological events. We address commonly asked questions such as: Can calcium imaging be used to characterize neurons with high firing rates? Can the fluorescent signal report a decrease in spiking activity? What is the evidence that calcium transients in subcellular compartments correspond to distinct presynaptic axonal and postsynaptic dendritic events? By reviewing the empirical evidence and limitations, we suggest that, despite some caveats, calcium imaging is a versatile method to characterize a variety of neuronal events in vivo.
The curative effect of cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion

Ischemia and reperfusion of intestinal tissue (intestinal I/R) induce disruption of ileal contractility and chain responses of inflammatory. The aim of this study was to reveal whether therapeutic value of cannabinoid 2 (CB2) receptor activity in the intestinal I/R, via to the exogenous administration of CB2 agonist (AM‐1241). Intestinal I/R injury were performed through 30‐min ischemia and 150‐min reperfusion of mesenteric artery in Wistar rats. The pre‐administered doses of 0.1, 1, and 5 mg/kg of CB2 agonist were studied to inhibit inflammation of intestinal I/R injury including ileum smooth muscle contractility, polymorphonuclear cell migration, oxidant/antioxidant defense system, and provocative cytokines. Pre‐administration with CB2 receptor agonist ensured to consider improving the disrupted contractile responses in ileum smooth muscle along with decreased the formation of MDA that production of lipid peroxidation, reversed the depleted glutathione, inhibited the expression of TNF‐α and of IL‐1β in the intestinal I/R of rats. Taken together results of this research, the agonistic activity of CB2 receptor for healing of intestinal I/R injury is ensuring associated with anti‐inflammatory mechanisms such as the inhibiting of migration of inflammatory polymorphonuclear cells that origin of acute and initial responses of inflammation, the inhibiting of production of provocative and pro‐inflammatory cytokines like TNF‐α and IL‐1β, the rebalancing of oxidant/antioxidant redox system disrupted in injury of reperfusion period and the supporting of physiologic defensive systems in endothelial and inducible inflammatory cells.
Characterization of Aminoacyl-tRNA Synthetases in Chromerids

Aminoacyl-tRNA synthetases (AaRSs) are enzymes that catalyze the ligation of tRNAs to amino acids. There are AaRSs specific for each amino acid in the cell. Each cellular compartment in which translation takes place (the cytosol, mitochondria, and plastids in most cases), needs the full set of AaRSs; however, individual AaRSs can function in multiple compartments due to dual (or even multiple) targeting of nuclear-encoded proteins to various destinations in the cell. We searched the genomes of the chromerids, Chromera velia and Vitrella brassicaformis, for AaRS genes: 48 genes encoding AaRSs were identified in C. velia, while only 39 AaRS genes were found in V. brassicaformis. In the latter alga, ArgRS and GluRS were each encoded by a single gene occurring in a single copy; only PheRS was found in three genes, while the remaining AaRSs were encoded by two genes. In contrast, there were nine cases for which C. velia contained three genes of a given AaRS (45% of the AaRSs), all of them representing duplicated genes, except AsnRS and PheRS, which are more likely pseudoparalogs (acquired via horizontal or endosymbiotic gene transfer). Targeting predictions indicated that AaRSs are not (or not exclusively), in most cases, used in the cellular compartment from which their gene originates. The molecular phylogenies of the AaRSs are variable between the specific types, and similar between the two investigated chromerids. While genes with eukaryotic origin are more frequently retained, there is no clear pattern of orthologous pairs between C. velia and V. brassicaformis.