A potential alternative to fungicides using actives-free (meth)acrylate polymers for protection of wheat crops from fungal attachment and infection.

Fungicidal compounds are actives widely used for crop protection from fungal infection, but they can also kill beneficial organisms, enter the food chain and promote resistant pathogen strains from overuse. Here we report the first field crop trial of homopolymer materials that prevent fungal attachment, showing successful crop protection via an actives-free approach. In the trial, formulations containing two candidate polymers were applied to young wheat plants that were subject to natural infection with the wheat pathogen Zymoseptoria tritici. A formulation containing one of the candidate polymers, poly(di(ethylene glycol) ethyl ether acrylate) (abbreviated DEGEEA), produced a significant reduction (26%) in infection of the crop by Z. tritici, delivering protection against fungal infection that compared favourably with three different commercially established fungicide programmes tested in parallel. Furthermore, the sprayed polymers did not negatively affect wheat growth. The two lead polymer candidates were initially identified by bio-performance testing using in vitro microplate- and leaf-based assays and were taken forward successfully into a programme to optimize and scale-up their synthesis and compound them into a spray formulation. Therefore, the positive field trial outcome has also established the validity of the smaller-scale, laboratory-based bioassay data and scale-up methodologies used. Because fungal attachment to plant surfaces is a first step in many crop infections, this non-eluting polymer: (i) now offers significant potential to deliver protection against fungal attack, while (ii) addressing the fourth and aligning with the eleventh principles of green chemistry by using chemical products designed to preserve efficacy of function while reducing toxicity. A future focus should be to develop the material properties for this and other applications including other fungal pathogens.

Harnessing placebo: Lessons from psychedelic science.

The randomized controlled trial (RCT) research design assumes that a drug's "specific" effect can be isolated, added, and subtracted from the "nonspecific" effect of context and person. While RCTs are helpful in assessing the added benefit of a novel drug, they tend to obscure the curative potential of extra-pharmacological variables, known as "the placebo effect." Ample empirical evidence suggests that person/context-dependent physical, social, and cultural variables not only add to, but also shape drug effects, making them worth harnessing for patient benefits. Nevertheless, utilizing placebo effects in medicine is challenging due to conceptual and normative obstacles. In this article, we propose a new framework inspired by the field of psychedelic science and its employment of the "set and setting" concept. This framework acknowledges that drug and nondrug factors have an interactive and synergistic relationship. From it, we suggest ways to reintegrate nondrug variables into the biomedical toolbox, to ethically harness the placebo effect for improved clinical care.

Taping protocol for two presentations of pregnancy-related back pain: a case series.

BACKGROUND: Back pain is common during pregnancy and can have an adverse impact on the quality of life for some, yet treatment options for this population are limited. We document a chiropractic treatment that involves using kinesiology tape (tape) to help alleviate pregnancy-related back pain in two patients. CASE PRESENTATION AND MANAGEMENT: Two pregnant women reported to two different chiropractic offices with varying presentations of pregnancy-related back pain. A trial of chiropractic care was rendered in both chiropractic offices, which included the application of tape. OUTCOME AND DISCUSSION: In both case presentations, the addition of tape in the lumbosacral and/or abdominal regions, decreased pain intensity from 9-10/10 to 4/10 or less on the Numeric Rating Scale (NRS). Including a taping protocol to a plan of management in women with pregnancy-related LBP or PGP may be a safe and effective option to alleviate pain in this population.

CONTEXTE: Les maux de dos sont fréquents pendant la grossesse et peuvent avoir un impact négatif sur la qualité de vie de certaines femmes, mais les options de traitement pour cette population sont limitées. Nous documentons un traitement chiropratique qui implique l'utilisation de ruban de kinésiologie (ruban) pour aider à soulager les douleurs dorsales liées à la grossesse chez deux patientes. PRÉSENTATION ET GESTION DE CAS: Deux femmes enceintes se sont présentées à deux cabinets de chiropractie différents présentant des maux de dos différents liés à la grossesse. Un essai de soins chiropratiques comprenant l'application de ruban a été effectué dans les deux cabinets de chiropractie. RÉSULTATS ET DISCUSSION: Dans les deux présentations de cas, l'ajout de ruban dans les régions lombo-sacrées et/ou abdominales a diminué l'intensité de la douleur qui est passée de 9­10/10 à 4/10 ou moins sur l'échelle d'évaluation numérique (EEN). Le fait d'inclure un protocole d'utilisation de ruban à un plan de prise en charge chez les femmes présentant une lombalgie ou des douleurs pelviennes liées à la grossesse peut constituer une option sûre et efficace pour soulager la douleur chez cette population.

Fully hydrophobic HIV gp41 adopts a hemifusion-like conformation in phospholipid bilayers.

The HIV envelope glycoprotein mediates virus entry into target cells by fusing the virus lipid envelope with the cell membrane. This process requires large-scale conformational changes of the fusion protein gp41. Current understanding of the mechanisms with which gp41 induces membrane merger is limited by the fact that the hydrophobic N-terminal fusion peptide (FP) and C-terminal transmembrane domain (TMD) of the protein are challenging to characterize structurally in the lipid bilayer. Here we have expressed a gp41 construct that contains both termini, including the FP, the fusion peptide-proximal region (FPPR), the membrane-proximal external region (MPER), and the TMD. These hydrophobic domains are linked together by a shortened water-soluble ectodomain. We reconstituted this "short NC" gp41 into a virus-mimetic lipid membrane and conducted solid-state NMR experiments to probe the membrane-bound conformation and topology of the protein. 13C chemical shifts indicate that the C-terminal MPER-TMD is predominantly α-helical, whereas the N-terminal FP-FPPR exhibits ß-sheet character. Water and lipid 1H polarization transfer to the protein revealed that the TMD is well-inserted into the lipid bilayer, whereas the FPPR and MPER are exposed to the membrane surface. Importantly, correlation signals between the FP-FPPR and the MPER are observed, providing evidence that the ectodomain is sufficiently collapsed to bring the N- and C-terminal hydrophobic domains into close proximity. These results support a hemifusion-like model of the short NC gp41 in which the ectodomain forms a partially folded hairpin that places the FPPR and MPER on the opposing surfaces of two lipid membranes.

Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa).

BACKGROUND: Vascular endothelial growth factor A (VEGFA) is a major regulator of both physiological and pathological angiogenesis. Associations between polymorphisms in VEGFA and complex disease have been inconsistent. The parent from whom the allele was inherited may account for these inconsistencies. This study examined the parent of origin effect on the expression of murine Vegfa. METHODS: Two homozygous, inbred mouse strains A/J (AJ) and 129x1/SvJ (129) were crossed to produce reciprocal AJ129 and 129AJ offspring, respectively. RNA was extracted from cardiac tissue of 6 week old male (n = 8) and female (n = 8) parental, and male and female F1 offspring mice (AJ129 n = 8 and 129AJ n = 8). Vegfa and Hif1a expression levels were measured by qPCR and compared between the F1 offspring from the reciprocal crosses. RESULTS: We found significant differences in the expression of Vegfa in F1 offspring (AJ129 and 129AJ mice) of the reciprocal crosses between AJ and 129 mice. Offspring of male AJ mice had significantly higher expression of Vegfa than offspring of male 129 mice (p = 0.006). This difference in expression was not the result of preferential allele expression (allelic imbalance). Expression of Hif1a, a transcriptional regulator of Vegfa expression, was also higher in F1 offspring of an AJ father (p = 0.004). CONCLUSION: Differences in Vegfa and Hif1a gene expression are likely the result of an upstream angiogenic regulator gene that is influenced by the parent of origin. These results highlight the importance of including inheritance information, such as parent of origin, when undertaking allelic association studies.