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Bacillithiol (BSH) replaces glutathione (GSH) as the most prominent low-molecular-weight thiol in many low G + C gram-positive bacteria. BSH plays roles in metal binding, protein/ enzyme regulation, detoxification, redox buffering, and bacterial virulence. Given the small amounts of BSH isolated from natural sources and relatively lengthy chemical syntheses, the reactions of BSH with pertinent reactive oxygen, nitrogen, and sulfur species remain largely unexplored. We prepared BSH and exposed it to nitroxyl (HNO), a reactive nitrogen species that influences bacterial sulfur metabolism. The profile of this reaction was distinct from HNO oxidation of GSH, which yielded mixtures of disulfide and sulfinamide. The reaction of BSH and HNO (generated from Angeli’s salt) gives only sulfinamide products, including a newly proposed cyclic sulfinamide. Treatment of a glucosamine−cysteine conjugate, which lacks the malic acid group, with HNO forms disulfide, implicating the malic acid group in sulfinamide formation. This finding supports a mechanism involving the formation of an N-hydroxysulfenamide intermediate that dehydrates to a sulfenium ion that can be trapped by water or internally trapped by an amide nitrogen to give the cyclic sulfinamide. The biological relevance of BSH reactivity toward HNO is provided through in vivo experiments demonstrating that Bacillus subtilis exposed to HNO shows a growth phenotype, and a strain unable to produce BSH shows hypersensitivity toward HNO in minimal medium cultures. Thiol analysis of HNO-exposed cultures shows an overall decrease in reduced BSH levels, which is not accompanied by increased levels of BSSB, supporting a model involving the formation of an oxidized sulfinamide derivative, identified in vivo by high-pressure liquid chromatography/mass spectrometry. Collectively, these findings reveal the unique chemistry and biology of HNO with BSH in bacteria that produce this biothiol.more » « less
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As the largest-bodied member of the family Lemuridae and the presumed primary disperser of large seeds, Pachylemur, now extinct, was a critical member of Madagascar’s primate communities. Material of this genus has been found at almost all subfossil sites across Madagascar, but extensive samples of this taxon are known from very few. It has been one of the more historically neglected of the “giant” extinct lemurs, as it is not very different in morphology from its nearest extant relative, Varecia, except in body size. The flooded cave called Vintany at the Tsimanampesotse National Park in southwestern Madagascar has yielded numerous specimens of P. insignis, including whole skulls and mandibles, many isolated postcranial elements, and, importantly, partial associated skeletons of immature individuals. This material allows us to address previously unanswered questions regarding its paleobiology, including questions concerning its growth and development. This article focuses specifically on its life history profile (especially developmental sequences and life history-related traits such as Retzius line periodicity of the teeth and endocranial volume in adults). We ask to what extent, despite its larger size, did Pachylemur “grow” like its smaller-bodied relatives? Did its dental eruption sequence and index of Relative Retardation of the Replacement teeth resemble those of its closest relatives? Did it, like other lemurs, have a Retzius line periodicity that is lower than “expected” for a primate of its body size, and if so, what is the likely significance of this? Was its brain smaller than expected for a primate of its body size? For these and other questions, we evaluate how large-bodied lemurs differ from anthropoids of comparable body size.more » « less
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The Super-Kamiokande and T2K Collaborations present a joint measurement of neutrino oscillation parameters from their atmospheric and beam neutrino data. It uses a common interaction model for events overlapping in neutrino energy and correlated detector systematic uncertainties between the two datasets, which are found to be compatible. Using 3244.4 days of atmospheric data and a beam exposure of protons on target in (anti)neutrino mode, the analysis finds a exclusion of conservation (defined as ) and a exclusion of the inverted mass ordering. Published by the American Physical Society2025more » « lessFree, publicly-accessible full text available January 1, 2026