Haslundharvey2165

Cutaneous mold infections commonly result from an array of traumatic injuries that involve direct inoculation of contaminated soil into wounds. Here, we explored the use of antimicrobial blue light (aBL; 405nm wavelength) and the combination of aBL with quinine hydrochloride (aBL + Q-HCL) for the treatment of cutaneous mold infections.

Efficacy of aBL and aBL + Q-HCL in killing clinically important pathogenic molds (Aspergillus fumigatus, Aspergillus flavus, and Fusarium oxyprorum) was investigated. Ultra-performance liquid chromatography (UPLC) identified and quantified endogenous porphyrins in the mold conidia. Finally, a mouse model of dermabrasion wound infected with a bioluminescent variant of A. fumigatus was developed to investigate the efficacy of aBL in treating cutaneous mold infections.

We demonstrated that mold conidia are tolerant to aBL, but Q-HCL enhances efficacy. Transmission electron microscopy revealed intracellular damage by aBL. aBL + Q-HCL resulted in intracellular and cell wall damage. Porphyrins were observed in all mold strains, with A. fumigatus having the highest concentration. aBL and aBL + Q-HCL effectively reduced the burden of A. fumigatus within an established dermabrasion infection that limited recurrence post-treatment.

aBL and aBL + Q-HCL may offer a novel approach for the treatment of mold infections.

aBL and aBL + Q-HCL may offer a novel approach for the treatment of mold infections.

Botulinum toxin A (BTX-A) is a commonly used as neuromodulator in several neurological diseases and aesthetic indications. Formation of neutralizing antibodies (Nabs) after BTX-A injections may be responsible for treatment failure.

To quantify the prevalence of Nabs following treatment with Abobotulinumtoxin A (ABO), Incobotulinumtoxin A (INCO) and Onabotulinumtoxin A (ONA) for approved therapeutic indications.

An electronic systematic search (2000-2020) using Pubmed, Scopus, Web of science, and Embase was conducted. Original studies reporting prevalence of Nabs were included. Risk of bias was evaluated using cochrane and Newcastle-Ottawa scale tools. Data analysis was carried out through open meta-analyst and comprehensive meta-analysis softwares.

A total of 43 studies involving 8,833 patients were included in a meta-analysis. The incidence of NAbs was 1.8% (summary estimate= 0.018, 95% CI [0.012, 0.023]); A meta-regression analysis revealed that BTX-A duration was significantly associated with increement of such patients.In C4 species, β-carbonic anhydrase (CA), localized to the cytosol of the mesophyll cells, accelerates the interconversion of CO2 to HCO3-, the substrate used by phosphoenolpyruvate carboxylase (PEPC) in the first step of C4 photosynthesis. Here we describe the identification and characterization of low CO2-responsive mutant 1 (lcr1) isolated from an N-nitroso-N-methylurea- (NMU) treated Setaria viridis mutant population. Roscovitine mw Forward genetic investigation revealed that the mutated gene Sevir.5G247800 of lcr1 possessed a single nucleotide transition from cytosine to thymine in a β-CA gene causing an amino acid change from leucine to phenylalanine. This resulted in severe reduction in growth and photosynthesis in the mutant. Both the CO2 compensation point and carbon isotope discrimination values of the mutant were significantly increased. Growth of the mutants was stunted when grown under ambient pCO2 but recovered at elevated pCO2. Further bioinformatics analyses revealed that the mutation has led to functional changes in one of the conserved residues of the protein, situated near the catalytic site. CA transcript accumulation in the mutant was 80% lower, CA protein accumulation 30% lower, and CA activity ~98% lower compared with the wild type. Changes in the abundance of other primary C4 pathway enzymes were observed; accumulation of PEPC protein was significantly increased and accumulation of malate dehydrogenase and malic enzyme decreased. The reduction of CA protein activity and abundance in lcr1 restricts the supply of bicarbonate to PEPC, limiting C4 photosynthesis and growth. This study establishes Sevir.5G247800 as the major CA allele in Setaria for C4 photosynthesis and provides important insights into the function of CA in C4 photosynthesis that would be required to generate a rice plant with a functional C4 biochemical pathway.Aberrant differentiation of keratinocytes disrupts the skin barrier and causes a series of skin diseases. However, the molecular basis of keratinocyte differentiation is still poorly understood. In the present study, we examined the expression of C7ORF41 using tissue microarrays by immunohistochemistry and found that C7ORF41 is specifically expressed in the basal layers of skin epithelium and its expression is gradually decreased during keratinocytes differentiation. Importantly, we corroborated the pivotal role of C7ORF41 during keratinocyte differentiation by C7ORF41 knockdown or overexpression in TPA-induced Hacat keratinocytes. Mechanismly, we first demonstrated that C7ORF41 inhibited keratinocyte differentiation mainly through formatting a complex with IKKα in the cytoplasm, which thus blocked the nuclear translocation of IKKα. Furthermore, we also demonstrated that inhibiting the PKCα/ERK signaling pathway reversed the reduction in C7ORF41 in TPA-induced keratinocytes, indicating that C7ORF41 expression could be regulated by upstream PKCα/ERK signaling pathway during keratinocyte differentiation. Collectively, our study uncovers a novel regulatory network PKCα/ERK/C7ORF41/IKKα during keratinocyte differentiation, which provides potential therapeutic targets for skin diseases.Synechococcus are picocyanobacteria with a cosmopolitan distribution. They are capable of surviving in a wide variety of environmental conditions. Synechococcus have been isolated from the Chesapeake Bay during winter months, and they show an impressive tolerance to cold temperatures. Cold-adapted Synechococcus are unique and diverse, as they have complex phylogenetic lineages closely related to subalpine cluster II, Bornholm Sea cluster, CB7 cluster, and some novel lineages which are independent from summer estuarine strains in subcluster 5.2. CBW1002 and CBW1006 are the first complete genomes to represent Bornholm Sea cluster Synechococcus strains. They have some of the largest genomes among the Synechococcus (3.8 Mb) and share many unique and cryptic homologs which could give insight into their ability to tolerate such cold and dynamic conditions in the Chesapeake Bay estuary.