Metastability in zero-temperature dynamics: Statistics of attractors

The zero-temperature dynamics of simple models such as Ising ferromagnets provides, as an alternative to the mean-field situation, interesting examples of dynamical systems with many attractors (absorbing configurations, blocked configurations, zero-temperature metastable states). After a brief review of metastability in the mean-field ferromagnet and of the droplet picture, we focus our attention onto zero-temperature single-spin-flip dynamics of ferromagnetic Ising models. The situations leading to metastability are characterized. The statistics and the spatial structure of the attractors thus obtained are investigated, and put in perspective with uniform a priori ensembles. We review the vast amount of exact results available in one dimension, and present original results on the square and honeycomb lattices.Comment: 21 pages, 6 figures. To appear in special issue of JPCM on Granular Matter edited by M. Nicodem

Synthesis and Properties of a Compositional Series of MIL-53(Al) Metal-Organic Framework Crystal-Glass Composites

Metal-organic framework crystal-glass composites (MOF-CGCs) are materials in which a crystalline MOF is dispersed within a MOF glass. In this work, we explore the room temperature stabilization of the open-pore form of MIL-53(Al), usually observed at high-temperature, which occurs upon encapsulation within a ZIF-62(Zn) MOF glass matrix. A series of MOF-CGCs containing different loadings of MIL-53(Al) were synthesized and characterized using X-ray diffraction and nuclear magnetic resonance spectroscopy. An upper limit of MIL-53(Al) that can be stabilized in the composite was determined for the first time. The nanostructure of the composites was probed using pair distribution function analysis and scanning transmission electron microscopy. Notably, the distribution and integrity of the crystalline compo-nent in a sample series was determined, and these findings related to the MOF-CGC gas adsorption capacity in order to identify the optimal loading necessary for maximum CO2 sorption capacity.TDB would like to thank both the Royal Society for a University Research Fellowship (UF150021) and the Royal Society for a Research Grant (RG94426). CWA would like to thank the Royal Society for a PhD studentship (RG160498), and the Commonwealth Scientific and Industrial Research Council for additional support (C2017/3108). Both JH and TDB gratefully acknowledge the EPSRC (EP/R015481/1). AFS acknowledges EPSRC for a studentship award under the Doctoral Training Programme. AMB acknowledges the Royal Society for funding (RGF\EA\180092), as well as the Cambridge Trust for a Vice Chancellor’s Award (304253100). We extend our gratitude to Diamond Light Source, Rutherford Appleton Laboratory, UK, for access to Beamline I15-1 (EE20038-1) and access and support in the use of the electron Physical Science Imaging Centre (EM20195). SMC acknowledges the Henslow Research Fellowship at Girton College, Cambridge. PAM thanks the EPSRC for financial support under grant number EP/R025517/1

Cognitive impairment, fatigue and depression in multiple sclerosis: Is there a difference between benign and non-benign MS?

Available online 21 March 2023Introduction: Multiple Sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). The severity of disability in people with MS (PwMS) is generally measured with the Expanded Disability Status Scale (EDSS). A variant of MS known as ‘benign MS’ (BMS) has been defined as an EDSS score of 3 or lower, combined with a disease duration of 10 years or longer; however, there is disagreement in the field about whether BMS really exists. Given that the EDSS does not capture cognitive issues, communication dysfunction, fatigue, depression, or anxiety properly, its ability to accurately represent disability in all PwMS, including BMS, remains questionable. Methods: In this study, 141 persons with BMS (PwBMS) were included, consisting of 115 females (82%) and 26 males (18%) with a mean age of 50.8 (±8.68). A computerized test battery (NeuroTrax®) was used to assess cognition, covering seven cognitive domains (memory, executive function, visual-spatial processing, verbal function, attention, information processing, and motor skills). Fatigue was measured using the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was used to assess symptoms of depression. Cognitive impairment was defined for this study as when someone has a score lower than 85 in at least two subdomains of the cognitive test battery. Rates of impairment were compared to 158 persons with non-benign MS (PwNBMS; with a disease duration of 10 years and longer and an EDSS score higher than 3) and 487 PwMS with a disease duration of fewer than 10 years. Results: Cognitive impairment was found in 38% of PwBMS and in 66% of PwNBMS (p<0.001). In PwBMS, the lowest rate of impairment was found in the verbal function domain (18%) and the highest rate of impairment in the domain of information processing (32%). Fatigue and depression were found in 78% and 55% of all PwBMS, with no difference in these rates between PwBMS and PwNBMS (p = 0.787 and p = 0.316 resp.) Conclusion: Cognitive impairment, fatigue and depression are common among people with an EDSS-based definition of benign MS. These aspects should be incorporated into a new and better definition of truly benign MSHans Bogaardt, Daniel Golan, Marissa A Barrera, Stacie Attrill, Olivia Kaczmarek, Myassar Zarif, Barbara Bumstead, Marijean Buhse, Jeffrey Wilken, Glen M Doniger, Laura M Hancock, Iris-Katharina Penner, June Halper, Sarah A Morrow, Thomas J Covey, Mark Gudesblat

Regional differences in recombination hotspots between two chicken populations

<p>Abstract</p> <p>Background</p> <p>Although several genetic linkage maps of the chicken genome have been published, the resolution of these maps is limited and does not allow the precise identification of recombination hotspots. The availability of more than 3.2 million SNPs in the chicken genome and the recent advances in high throughput genotyping techniques enabled us to increase marker density for the construction of a high-resolution linkage map of the chicken genome. This high-resolution linkage map allowed us to study recombination hotspots across the genome between two chicken populations: a purebred broiler line and a broiler × broiler cross. In total, 1,619 animals from the two different broiler populations were genotyped with 17,790 SNPs.</p> <p>Results</p> <p>The resulting linkage map comprises 13,340 SNPs. Although 360 polymorphic SNPs that had not been assigned to a known chromosome on chicken genome build WASHUC2 were included in this study, no new linkage groups were found. The resulting linkage map is composed of 31 linkage groups, with a total length of 3,054 cM for the sex-average map of the combined population. The sex-average linkage map of the purebred broiler line is 686 cM smaller than the linkage map of the broiler × broiler cross.</p> <p>Conclusions</p> <p>In this study, we present a linkage map of the chicken genome at a substantially higher resolution than previously published linkage maps. Regional differences in recombination hotspots between the two mapping populations were observed in several chromosomes near the telomere of the p arm; the sex-specific analysis revealed that these regional differences were mainly caused by female-specific recombination hotspots in the broiler × broiler cross.</p

The Role of Sialyl Glycan Recognition in Host Tissue Tropism of the Avian Parasite Eimeria tenella

Eimeria spp. are a highly successful group of intracellular protozoan parasites that develop within intestinal epithelial cells of poultry, causing coccidiosis. As a result of resistance against anticoccidial drugs and the expense of manufacturing live vaccines, it is necessary to understand the relationship between Eimeria and its host more deeply, with a view to developing recombinant vaccines. Eimeria possesses a family of microneme lectins (MICs) that contain microneme adhesive repeat regions (MARR). We show that the major MARR protein from Eimeria tenella, EtMIC3, is deployed at the parasite-host interface during the early stages of invasion. EtMIC3 consists of seven tandem MAR1-type domains, which possess a high specificity for sialylated glycans as shown by cell-based assays and carbohydrate microarray analyses. The restricted tissue staining pattern observed for EtMIC3 in the chicken caecal epithelium indicates that EtMIC3 contributes to guiding the parasite to the site of invasion in the chicken gut. The microarray analyses also reveal a lack of recognition of glycan sequences terminating in the N-glycolyl form of sialic acid by EtMIC3. Thus the parasite is well adapted to the avian host which lacks N-glycolyl neuraminic acid. We provide new structural insight into the MAR1 family of domains and reveal the atomic resolution basis for the sialic acid-based carbohydrate recognition. Finally, a preliminary chicken immunization trial provides evidence that recombinant EtMIC3 protein and EtMIC3 DNA are effective vaccine candidates

Eimeripain, a Cathepsin B-Like Cysteine Protease, Expressed throughout Sporulation of the Apicomplexan Parasite Eimeria tenella

The invasion and replication of Eimeria tenella in the chicken intestine is responsible for avian coccidiosis, a disease that has major economic impacts on poultry industries worldwide. E. tenella is transmitted to naïve animals via shed unsporulated oocysts that need contact with air and humidity to form the infectious sporulated oocysts, which contain the first invasive form of the parasite, the sporozoite. Cysteine proteases (CPs) are major virulence factors expressed by protozoa. In this study, we show that E. tenella expresses five transcriptionally regulated genes encoding one cathepsin L, one cathepsin B and three cathepsin Cs. Biot-LC-LVG-CHN2, a cystatin derived probe, tagged eight polypeptides in unsporulated oocysts but only one in sporulated oocysts. CP-dependant activities were found against the fluorescent substrates, Z-FR-AMC and Z-LR-AMC, throughout the sporulation process. These activities corresponded to a cathepsin B-like enzyme since they were inhibited by CA-074, a specific cathepsin B inhibitor. A 3D model of the catalytic domain of the cathepsin B-like protease, based on its sequence homology with human cathepsin B, further confirmed its classification as a papain-like protease with similar characteristics to toxopain-1 from the related apicomplexan parasite, Toxoplasma gondii; we have, therefore, named the E. tenella cathepsin B, eimeripain. Following stable transfection of E. tenella sporozoites with a plasmid allowing the expression of eimeripain fused to the fluorescent protein mCherry, we demonstrated that eimeripain is detected throughout sporulation and has a punctate distribution in the bodies of extra- and intracellular parasites. Furthermore, CA-074 Me, the membrane-permeable derivative of CA-074, impairs invasion of epithelial MDBK cells by E. tenella sporozoites. This study represents the first characterization of CPs expressed by a parasite from the Eimeria genus. Moreover, it emphasizes the role of CPs in transmission and dissemination of exogenous stages of apicomplexan parasites