Comparison of clinical cure rates from footrot and contagious ovine digital dermatitis using zinc sulphate foot bathing and topical oxytetracycline: A randomised trial.

BACKGROUND: This study reports the clinical cure rates of topical oxytetracycline and 10% zinc sulphate foot bathing for treatment of interdigital dermatitis (ID), footrot (FR) and contagious ovine digital dermatitis (CODD) in lambs. METHODS: The study was a randomised controlled trial of 75 lambs. Group A (n = 38) was foot bathed daily for 5 days in 10% zinc sulphate for 15 minutes and group B was treated with daily topical oxytetracycline for 5 days. On days 0, 7, 14, 28 and 42, lambs were scored for locomotion and foot lesions were recorded. RESULTS: The initial cure rates for ID were 96.20% and 97.00%; for FR, 100% and 95%; and for CODD, 90.09% and 83.33% for zinc sulphate and oxytetracycline, respectively. By day 42, these had changed to 53.16% and 61% for ID; 47.82% and 70% for FR; and 100% and 83.33% for CODD. There were no significant differences in cure rates between the treatments for most time points. LIMITATIONS: The sample size was small, and further studies in larger cohorts and different classes of sheep are required before the findings can be translated into recommendations for clinical practice. CONCLUSION: Both treatments achieved cure rates that are comparable to reported cure rates using systemic antibiotics and could be an effective alternative.

The Proposal.

While the connection between arts, culture, and public health is not new, intentional efforts toward cross-sector collaboration in these areas are being lifted as timely and transformative. This is a call to artists, creatives, culture bearers, and activators. This is a call to public health practitioners, doctors, educators, and the myriad of peoples whose work touches the public's health. In this piece, I propose a marriage of these two seemingly disparate disciplines-arts and public health-their actors and engagements. In this piece, I propose this marriage as dance, as movement, as evolution, even revolution. What could our world look like if more of the people and the sectors of arts and public health worked together to advance our most pressing public health priorities? I offer this work to help us imagine the possibilities of growing this intentional collaboration. This piece both proposes and marries; iterates and exemplifies. By presenting this work as poetry, I propose that art not be the afterthought, the accent, the cherry on top as we strive to address public health issues, a multitude exacerbated and illuminated in the face of COVID-19. I posit that art is the consistency, the substance, the forethought, and a vehicle through which we can come to realize the positive change that we hope to see. As we ponder our next potential public health engagements, know this. Not only can this marriage soothe us and move us; but it can literally improve us. This is the proposal. Will you accept?To view the original version of this poem, see the supplemental material section of this article online.

Biosynthesis of lycosantalonol, a cis-prenyl derived diterpenoid.

Terpenoid natural products are generally derived from isoprenyl diphosphate precursors with trans double-bond configuration, and no diterpenoid derived from the cisoid precursor (Z,Z,Z)-nerylneryl diphosphate (1) has yet been identified. Here further investigation of a terpenoid biosynthetic gene cluster from tomato is reported, which resulted in identification of a biosynthetic pathway from 1, in a pathway featuring a number of interesting transformations. Compound 1 is first cyclized to a tricyclene core ring structure analogous to that found in α-santalene, with the resulting diterpene termed here lycosantalene (2). Quantum chemical calculations indicate a role for the diphosphate anion coproduct in this cyclization reaction. Subsequently, the internal cis double bond of the neryl side chain in 2 is then further transformed to an α-hydroxy ketone moiety via an epoxide intermediate (3). Oxygen labeling studies indicate 3 undergoes oxidative conversion to lycosantalonol (4). Thus, in addition to elucidating the cisoid origins of 4, this work has further provided mechanistic insight into the interesting transformations required for its production.

Biochemical characterization of the castor bean ent-kaurene synthase(-like) family supports quantum chemical view of diterpene cyclization.

It has become apparent that plants have extensively diversified their arsenal of labdane-related diterpenoids (LRDs), in part via gene duplication and neo-functionalization of the ancestral ent-kaurene synthase (KS) required for gibberellin metabolism. For example, castor bean (Ricinus communis) was previously shown to produce an interesting set of biosynthetically related diterpenes, specifically ent-sandracopimaradiene, ent-beyerene, and ent-trachylobane, in addition to ent-kaurene, using four separate diterpene synthases, albeit these remain unidentified. Notably, despite mechanistic similarity of the underlying reaction to that catalyzed by KSs, ent-beyerene and ent-trachylobane synthases have not yet been identified. Given our interest in LRD biosynthesis, and the recent availability of the castor bean genome sequence, a synthetic biology approach was applied to biochemically characterize the four KS(-like) enzymes [KS(L)s] found in Ricinus communis [i.e., the RcKS(L)s]. In particular, using bacteria engineered to produce the relevant ent-copalyl diphosphate precursor and synthetic genes based on the predicted RcKS(L)s, although this ultimately required correction of a "splicing" error in one of the predicted genes, highlighting the dependence of such a synthetic biology approach on accurate gene sequences. Nevertheless, it is possible to assign each of the four RcKS(L)s to one of the previously observed diterpene synthase activities, providing access to functionally enzymes. Intriguingly, the product distribution of the RcKS(L)s seems to support the distinct diterpene synthase reaction mechanism proposed by quantum chemical calculations, rather than the classically proposed pathway.

Combining metabolomics and transcriptomics to characterize tanshinone biosynthesis in Salvia miltiorrhiza.

BACKGROUND: Plant natural products have been co-opted for millennia by humans for various uses such as flavor, fragrances, and medicines. These compounds often are only produced in relatively low amounts and are difficult to chemically synthesize, limiting access. While elucidation of the underlying biosynthetic processes might help alleviate these issues (e.g., via metabolic engineering), investigation of this is hindered by the low levels of relevant gene expression and expansion of the corresponding enzymatic gene families. However, the often-inducible nature of such metabolic processes enables selection of those genes whose expression pattern indicates a role in production of the targeted natural product. RESULTS: Here, we combine metabolomics and transcriptomics to investigate the inducible biosynthesis of the bioactive diterpenoid tanshinones from the Chinese medicinal herb, Salvia miltiorrhiza (Danshen). Untargeted metabolomics investigation of elicited hairy root cultures indicated that tanshinone production was a dominant component of the metabolic response, increasing at later time points. A transcriptomic approach was applied to not only define a comprehensive transcriptome (comprised of 20,972 non-redundant genes), but also its response to induction, revealing 6,358 genes that exhibited differential expression, with significant enrichment for up-regulation of genes involved in stress, stimulus and immune response processes. Consistent with our metabolomics analysis, there appears to be a slower but more sustained increased in transcript levels of known genes from diterpenoid and, more specifically, tanshinone biosynthesis. Among the co-regulated genes were 70 transcription factors and 8 cytochromes P450, providing targets for future investigation. CONCLUSIONS: Our results indicate a biphasic response of Danshen terpenoid metabolism to elicitation, with early induction of sesqui- and tri- terpenoid biosynthesis, followed by later and more sustained production of the diterpenoid tanshinones. Our data provides a firm foundation for further elucidation of tanshinone and other inducible natural product metabolism in Danshen.