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Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis but its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as novel candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients and describe two novel mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.

This introductory article argues for making food central to a praxis of cultural studies in the transhispanic world and the importance of inserting Hispanist voices into the arena of food studies s...

Spanish writer Carmen de Burgos’ popular fiction and essays reveal her to be one of Spain’s most influential early feminists, a fact complicated by her publication of cookbooks La cocina moderna (1...

Dana Island (ancient Pityoussa) is the largest island of the Tasucu Gulf in Rough Cilicia (Turkey). It is strategically located ca. 2.5 km off the shores of the rugged mainland along an ancient mar...

The Burkholderia genus encompasses many Gram-negative bacteria living in the rhizosphere. Some Burkholderia species can cause life-threatening human infections, highlighting the need for clinical interventions targeting specific lipopolysaccharide proteins. Burkholderia cenocepacia O-linked protein glycosylation has been reported, but the chemical structure of the O-glycan and the machinery required for its biosynthesis are unknown and could reveal potential therapeutic targets. Here, using bioinformatics approaches, gene-knockout mutants, purified recombinant proteins, LC-MS–based analyses of O-glycans, and NMR-based structural analyses, we identified a B. cenocepacia O-glycosylation (ogc) gene cluster necessary for synthesis, assembly, and membrane translocation of a lipid-linked O-glycan, as well as its structure, which consists of a β-Gal-(1,3)–α-GalNAc-(1,3)–β-GalNAc trisaccharide. We demonstrate that the ogc cluster is conserved in the Burkholderia genus, and we confirm the production of glycoproteins with similar glycans in the Burkholderia species: B. thailandensis, B. gladioli, and B. pseudomallei. Furthermore, we show that absence of protein O-glycosylation severely affects bacterial fitness and accelerates bacterial clearance in a Galleria mellonella larva infection model. Finally, our experiments revealed that patients infected with B. cenocepacia, Burkholderia multivorans, B. pseudomallei, or Burkholderia mallei develop O-glycan–specific antibodies. Together, these results highlight the importance of general protein O-glycosylation in the biology of the Burkholderia genus and its potential as a target for inhibition or immunotherapy approaches to control Burkholderia infections.

Chimpanzees, like all great ape species, have experienced a dramatic decline in global numbers during the past decades. The degradation, fragmentation and loss of suitable habitat impede chimpanzee movements, reducing the potential for dispersal and thus population viability. In Tanzania, 90% of the 2000–3000 remaining chimpanzees are found within the Greater Mahale Ecosystem (GME), the majority of which live at low densities outside of national park boundaries. Recent genetic analyses have identified potential boundaries between the northern and southern populations of the GME. Using landscape connectivity modelling, we aimed to clarify population connectivity across this vast ecosystem (>20,000 km2) and assess change over time. We developed habitat suitability models to create an index of habitat selection by chimpanzees and mapped connectivity using circuit theory. Our results suggest that, in recent history (1973), the entire ecosystem was linked by a series of corridors showing a high likelihood of chimpanzee movement. Our analysis also reveals a reduction of connectivity by 2017 impacting the two corridors linking the northern and southern GME. When projected to 2027, areas contributing to connectivity are predicted to continue to decline, threatening all available corridors between the northern and southern GME. By modelling connectivity across time, we were able to identify key areas to focus conservation efforts to maintain population viability within the largest chimpanzee population in Tanzania.

Inflammasomes are cytosolic multiprotein complexes that assemble in response to various stimuli. Activated inflammasomes process pro-IL-1β and pro-IL-18 into bioactive forms. inflammasome-derived IL-1β initiates epithelial cell and fibroblast proliferation. Thus, inflammasomes might also be decisive key drivers through activating and recruiting cells required for efficient tissue repair. However, their exact function in lung tissue damage and repair are unclear. C57BL/6, NLRP3−/− and Caspase1/11−/− mice were treated with 40μg LPS by intratracheal instillation to induce lung injury. Lungs and BALF were collected for histological scoring, cytokine analysis and inflammasome marker expression by IHC, immunoblotting and ELISA. The Lung injury score of LPS treated mice was increased on day 1 and 3 but reverted to nearly normal on day 7. NLRP3 deficiency did not alter lung damage indicating that the NLRP3 inflammasome might not be an essential mediator of injury in this model. LPS induced lung epithelial type 2 cell damage was shown by decreased Pro-SPC expression, which was associated with increased expression of inflammasome markers (ASC, NLRC4, and NLRP3) and pro-IL-1β. Immune cells and more specifically CD68+ macrophages and Ly6G/C+ neutrophils were the predominant cell types expressing inflammasome markers. Caspase1/11−/− mice had reduced IL-1β levels in BALF compared to LPS-treated C57BL/6 mice indicating a potential role of inflammasomes in response to tissue damage. However, both NLRP3−/− and caspase1/11−/− mice had no significant change in CXCL1/KC levels in BALF compared to C57BL/6 mice on Day 3 and 7 of the acute lung injury model. Further investigations will reveal the impact of inflammasome activity on tissue repair.

Carmen de Burgos fiction comprises ten full-length novels and more than eighty melodramatic novellas; her nonfiction includes high-profile essays on women's rights, a lengthy feminist treatise and twenty-seven practical manuals on topics ranging from seduction to cooking. The culinary education she proposes closely resembles feminist efforts elsewhere in the West to re-define domestic tasks into the field of home economics. Home economics allowed women to assume a professionalized role outside the home and gave them a role in public policy, expanding their housekeeping from the home to social and municipal contexts. Like the United States (US)-American home economists, Spanish women would be prepared to address cooking and nutrition as part of social policy, by working to improve "the material conditions of the popular class". Providing women a culinary education, Burgos argues, has the potential to strengthen the nation's public health and hygiene and improve the material conditions of Spain's working class.

Excavations at Yenikapi in Istanbul, Turkey, related to the Marmaray Project, have unearthed remains of Constantinople's Theodosian Harbour, including 37 Byzantine shipwrecks of 5th- to 11th-century date. Eight of these shipwrecks, six round ships and two of the first long ships, or galleys, to be excavated from the Byzantine period, were studied by archaeologists from the Institute of Nautical Archaeology. These well-preserved shipwrecks are an important new source of information on the maritime commerce of Constantinople and the gradual shift from shell-based to skeleton-based shipbuilding in the Mediterranean during the second half of the first millennium AD.

This article examines Emilia Pardo Bazan's La cocina espanola antigua (1913) and La cocina espanola moderna (1914/1917) as a culinary-philological project coherent with wider nation-building discourses. Her project also reveals the class divisions at the heart of Spanish liberal nationalism. In La cocina espanola antigua she authenticates her recipes by referring them to an idealized pueblo, the Volk, whose practices must be recorded as evidence of longstanding culinary traditions. She illustrates the transition identified by Derek Flitter from this Volk pueblo to the pueblo as ‘a pro-active political subject’ in comparison to her ‘Cartas de la Condesa’ article (October 1911), which configures cooking as a philological practice and an escape from a radical working class. Thus the modern cuisine she presents in La cocina espanola moderna becomes a practice of anxious middleclassness in which she substitutes bourgeois elegance for tradition as the defining characteristic of Spain's national prominence.

Klebsiella pneumoniae is an important cause of multidrug‐resistant infections worldwide. Recent studies highlight the emergence of multidrug‐resistant K. pneumoniae strains which show resistance to colistin, a last‐line antibiotic, arising from mutational inactivation of the mgrB regulatory gene. However, the precise molecular resistance mechanisms of mgrB‐associated colistin resistance and its impact on virulence remain unclear. Here, we constructed an mgrB gene K. pneumoniae mutant and performed characterisation of its lipid A structure, polymyxin and antimicrobial peptide resistance, virulence and inflammatory responses upon infection. Our data reveal that mgrB mutation induces PhoPQ‐governed lipid A remodelling which confers not only resistance to polymyxins, but also enhances K. pneumoniae virulence by decreasing antimicrobial peptide susceptibility and attenuating early host defence response activation. Overall, our findings have important implications for patient management and antimicrobial stewardship, while also stressing antibiotic resistance development is not inexorably linked with subdued bacterial fitness and virulence.