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Plant pathogens and pests can cause significant losses in crop yields, affecting food security and the global economy. Many traditional chemical pesticides are used to combat these organisms. This can lead to the development of pesticide-resistant strains of pathogens/insects and negatively impact the environment. The development of new bioprotectants, which are less harmful to the environment and less likely to lead to pesticide-resistance, appears as a sustainable strategy to increase plant immunity. Natural Rhamnolipids (RL-Nat) are a class of biosurfactants with bioprotectant properties that are produced by an opportunistic human pathogen bacterium. RL-Nat can act as plant resistance inducers against a wide variety of pathogens. Recently, a series of bioinspired synthetic mono-RLs produced by green chemistry were also reported as phytoprotectants. Here, we explored their capacity to generate novel colloidal systems that might be used to encapsulate bioactive hydrophobic compounds to enhance their performance as plant bioprotectants. The synthetic mono-RLs showed good surfactant properties and emulsification power providing stable nanoemulsions capable of acting as bio-carriers with good wettability. Synthetic RLs-stabilized nanoemulsions were more effective than RLs suspensions at inducing plant immunity, without causing deleterious effects. These nanoemulsions were innocuous to native substrate microbiota and beneficial soil-borne microbes, making them promising safe bio-carriers for crop protection.

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The effectiveness of haploid induction systems is regarded not only for high haploid induction rate (HIR) but also resource savings. Isolation fields are proposed for hybrid induction. However, efficient haploid production depends on inducer traits such as high HIR, abundant pollen production, and tall plants. Seven hybrid inducers and their respective parents were evaluated over three years for HIR, seeds set in cross-pollinations, plant and ear height, tassel size, and tassel branching. Mid-parent heterosis was estimated to quantify how much inducer traits improve in hybrids in comparison to their parents. Heterosis benefits hybrid inducers for plant height, ear height, and tassel size. Two hybrid inducers, BH201/LH82-Ped126 and BH201/LH82-Ped128, are promising for haploid induction in isolation fields. Hybrid inducers offer convenience and resource-effectiveness for haploid induction by means of improving plant vigor without compromising HIR.

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Phosphites have been used as inducers of resistance, activating the defense of plants and increasing its ability to respond to the invasion of the pathogen. However, the mode of action of phosphites in defense responses has not yet been fully elucidated. The objective of this study was to evaluate the effect of potassium phosphite (KPhi) in coffee cultivars with different levels of resistance to rust to clarify the mechanism by which KPhi activates the constitutive defense of plants. To this end, we studied the expression of genes and the activity of enzymes involved in the defense pathway of salicylic acid (SA) and reactive oxygen species (ROS), in addition to the levels of total soluble phenolic compounds and soluble lignin. Treatment with KPhi induced constitutive defense responses in cultivars resistant and susceptible to rust. The results suggest that KPhi acts in two parallel defense pathways, SA and ROS, which are essential for the induction of systemic acquired resistance (SAR) when activated simultaneously. The activation of the mechanisms associated with defense routes demonstrates that KPhi is a potential inducer of resistance in coffee plants.

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We used the Langmuir monolayers technique to study the surface properties of melittin toxin mixed with either liquid-condensed DSPC or liquid-expanded POPC phospholipids. Pure melittin peptide forms stable insoluble monolayers at the air-water interface without interacting with Thioflavin T (Th-T), a sensitive probe to detect protein amyloid formation. When melittin peptide is mixed with DSPC lipid at 50 % of peptide area proportion at the surface, we observed the formation of fibril-like structures detected by Brewster angle microscopy (BAM), but they were not observable with POPC. The nano-structures in the melittin-DSPC mixtures became Th-T positive labeling when the arrangement was observed with fluorescence microscopy. In this condition, Th-T undergoes an unexpected shift in the typical emission wavelength of this amyloid marker when a 2D fluorescence analysis is conducted. Even when reflectivity analysis of BAM imaging evidenced that these structures would correspond to the DSPC lipid component of the mixture, the interpretation of ATR-FTIR and Th-T data suggested that both components were involved in a new lipid-peptide rearrangement. These nano-fibril arrangements were also evidenced by scanning electron and atomic force microscopy when the films were transferred to a mica support. The fibril formation was not detected when melittin was mixed with the liquid-expanded POPC lipid. We postulated that DSPC lipids can dynamically trigger the process of amyloid-like nano-arrangement formation at the interface. This process is favored by the relative peptide content, the quality of the interfacial environment, and the physical state of the lipid at the surface.

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Metal solubilization from discarded electrical material and electronic devices (e-waste) using the bioleaching capabilities of bacterial cells is highly effective. However, gaps in understanding about the microbiological processes involved in the bioleaching reaction leads to less efficient metal solubilization in large-scale e-waste processing. In this study, bacterial species belonging to the genera Acidithiobacillus and Pseudomonas were used to leach copper and gold from discarded printed circuit boards (PCB). Through modulation of the cell-to-cell communication system in these bacteria, phenotypic traits directly involved in the bioleaching reaction were regulated in order to improve the metal solubilization. Addition of the long chain synthetic autoinducer molecule N-acyl homoserine lactone (AHL) of the quorum sensing pathway to the bioleaching reaction resulted in a significant enhancement of metal extraction from PCB. Factors such as: cell attachment to PCB, biofilm formation and hydrogen cyanide (HCN) production were regulated by the quorum sensing system and could be directly related to the improvement of metal bioleaching. Bioleaching reactions using bacterial quorum sensing modulation could represent a valuable tool in overcoming limitations at the industrial level imposed by microbiological traits that lead to inefficient metal bioleaching from e-waste.

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Doubled haploid technology is a feasible, fast, and cost-efficient way of producing completely homozygous lines in maize. Many factors contribute to the success of this system including the haploid induction rate (HIR) of inducer lines, the inducibility of donor background, and environmental conditions. Sixteen inducer lines were tested on eight different genetic backgrounds of five categories in different environments for the HIR to determine possible interaction specificity. The HIR was assessed using the R1-nj phenotype and corrected using the red root marker or using a gold-standard test that uses plant traits. RWS and Mo-17-derived inducers showed higher average induction rates and the commercial dent hybrid background showed higher inducibility. In contrast, sweet corn and flint backgrounds had a relatively lower inducibility, while non-stiff stalk and stiff stalk backgrounds showed intermediate inducibility. For the poor-performing donors (sweet corn and flint), there was no difference in the HIR among the inducers. Anthocyanin inhibitor genes in such donors were assumed to have increased the misclassification rate in the F1 fraction and, hence, result in a lower HIR.

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AIM: This study was designed to investigate if culturing nematophagous fungi (NF) in the presence of a Haemonchus contortus larva crude extract (HcCE) enhances the nematocidal activity of nematophagous fungi liquid culture filtrates (NFCF). MATERIALS AND METHODS: Four NF Arthrobotrys oligospora, A. musiformis, Duddingtonia flagrans and Clonostachys rosea were cultured in flasks (n = 5) containing Czapek-Dox broth medium (CDB) in the presence or absence of HcCE. NFCF recovered by filtration of each fungus (200 mg/mL) were assessed on H. contortus infective larvae (L3) using 96-well micro-titer plates (n = 4). Additionally, CDB and water were considered negative controls, while Ivermectin acted as a positive control. After 48 h confrontation, ten 10-µL aliquots of each well were deposited on slides and observed under the microscope (40 ×). Dead and alive larvae in the aliquots were quantified, and a mortality rate (MR) was estimated. RESULTS: The MR of the different NFCF was greatly enhanced by the presence of HcCE. The four NF incubated in the absence of HcCE showed low mortality percentages from 8.2 to 25.8%; in contrast, when the assessed NF growth in the presence of HcCE showed a lethal activity ranging from 66.8 to 80.5%. Only C. rosea showed a moderate increase in the presence of the elicitor (42.7%). CONCLUSION: This study shows evidence about the HcCE enhances the production of nematocidal activity in NFCF. Future studies should be performed to elucidate the compounds responsible of the nematocidal activity that could have important implications in the control of sheep haemonchosis.

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One of the goals in recombinant protein production in Escherichia coli is to maximize productivity. High volumetric and specific yields can be reached after careful selection of expression strains and optimization of cultivation parameters. In this chapter, we review the many tools available to make the most out of this versatile microbial cell factory. Useful guidelines and options for troubleshooting production are presented.

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Background: Visceral leishmaniasis (VL) is caused by Leishmania infantum or L. donovani infection. One of the main problems related to this disease is the emergence of severe clinical forms with a lethality of 5-20%, even while under specific treatment. In humans and other species susceptible to fatal VL, such as dogs and hamsters, the disruption of splenic white pulp (WP) is accompanied by disease progression. Control of VL progression is seen in BALB/c mice, as evidenced by a mild clinical presentation and controlled parasite replication in the liver and spleen. In this study, we investigated the features involved in the morphological remodeling of splenic compartments associated with the control of VL progression to death. Methods: We evaluated cohorts of BALB/c mice after 30, 60, and 90 days of infection by L. infantum. Spleen morphology, cell population subsets and cytokine production were studied in the spleen using flow- and histo-cytometry. Results: Intraperitoneal infection with 108 promastigotes of L. infantum led to progressive increases in spleen size at 60 and 90 days after infection. Splenomegaly was the only clinical sign of disease observed. At 30 days after infection, hyperplasia in the WP and decreased numbers of plasmacytoid dendritic cells were observed. The WP hyperplasia subsided at 60 days post-infection. However, the splenomegaly remained in association with increased numbers of macrophages, B and T lymphocytes and plasma cells. An increased number of lymphoid tissue inducer (LTi) cells was observed; these were distributed around the periarteriolar lymphoid sheath in control mice and scattered throughout the red pulp in the Leishmania-infected mice. After 90 days of infection, increased IL-6 and IFN-γ production was seen in the spleen, as well as higher frequencies of follicular and plasmacytoid dendritic cells. Conclusion: The data presented herein emphasizes the potential role of spleen remodeling in the control of severe forms of VL and highlights features potentially involved in this process.

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The prediction of regulatory single nucleotide polymorphisms (rSNPs) in proximal promoters of disease-related genes could be a useful tool for personalized medicine in both patient stratification and customized therapy. Using our previously reported method of rSNPs prediction (currently a software called SNPClinic v.1.0) as well as with PredictSNP tool, we performed in silico prediction of regulatory SNPs in the antimicrobial peptide human ß-defensin 1 gene in three human cell lines from 1,000 Genomes Project (1kGP), namely A549 (epithelial cell line), HL-60 (neutrophils) and TH 1 (lymphocytes). These predictions were run in a proximal pseudo-promoter comprising all common alleles on each polymorphic site according to the 1,000 Genomes Project data (1kGP: ALL). Plasmid vectors containing either the major or the minor allele of a putative rSNP rs5743417 (categorized as regulatory by SNPClinic and confirmed by PredictSNP) and a non-rSNP negative control were transfected to lung A549 human epithelial cell line. We assessed functionality of rSNPs by qPCR using the Pfaffl method. In A549 cells, minor allele of the SNP rs5743417 G→A showed a significant reduction in gene expression, diminishing DEFB1 transcription by 33% when compared with the G major allele (p-value = .03). SNP rs5743417 minor allele has high frequency in Gambians (8%, 1kGP population: GWD) and Afro-Americans (3.3%, 1kGP population: ASW). This SNP alters three transcription factors binding sites (TFBSs) comprising SREBP2 (sterols and haematopoietic pathways), CREB1 (cAMP, insulin and TNF pathways) and JUND (apoptosis, senescence and stress pathways) in the proximal promoter of DEFB1. Further in silico analysis reveals that this SNP also overlaps with GS1-24F4.2, a lincRNA gene complementary to the X Kell blood group related 5 (XKR5) mRNA. The potential clinical impact of the altered constitutive expression of DEFB1 caused by rSNP rs5743417 in DEFB1-associated diseases as tuberculosis, COPD, asthma, cystic fibrosis and cancer in African and Afro-American populations deserves further research.

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Green fluorescent protein (GFP) is a globular protein used as biosensor and biomarker in medical and industrial fields. However, due to the expensive production costs of expressing proteins using high-cost inducers like isopropyl-ß-d-1-thiogalactopyranoside (IPTG), the number of GFP applications are still scarce. This work studied the production of enhanced GFP (EGFP) using Escherichia coli BL21 (DE3) [pLysS; pET28(a)], aiming to increase its yield and reduce costs. First, the influence of agitation rate, induction time, and concentration of IPTG in the production of EGFP was evaluated, but only the first two parameters were significant. Subsequently, aiming to reduce costs related to the use of inducer, the IPTG concentration (0.005, 0.010, and 0.025 mM) was decreased and, interestingly, the production levels were maintained or increased. These results show that a proper choice of production conditions, particularly through the decrease of inducer concentration, is effective to reduce the upstream production costs and guarantee high EGFP expression.

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O tratamento de sementes (TS) é uma importante ferramenta no manejo de doenças na cultura do trigo, embora poucos produtos sejam indicados para esse fim. Por isso, a pesquisa deve realizar trabalhos relacionados à efetividade de diferentes produtos no TS e também o possível efeito fitotóxico. Os objetivos deste trabalho foram realizar testes fisiológicos em sementes e avaliar o desenvolvimento de duas cultivares de trigo (BRS Guamirim e TBIO Toruk), submetidas a 13 diferentes tratamentos de sementes. Para cada tratamento foram analisados a germinação e o vigor. As sementes tratadas também foram semeadas a campo, onde se determinou a emergência a campo e massa fresca de raiz e parte aérea. As sementes tratadas com azoxistrobina e Bacillus amyloliquefaciens resultaram em decréscimo na germinação da cultivar TBIO Toruk. Na análise do vigor houve diferença entre os tratamentos testados para as duas cultivares, sendo que houve redução do vigor em sementes tratadas com dimetomorfe para TBIO Toruk e azoxistrobina para a cultivar BRS Guamirim. As sementes submetidas ao tratamento Carboxamida A resultaram em plântulas com maiores valores de massa fresca de raiz e parte aérea. Os resultados apresentados permitem a seleção de produtos com baixa ou ausência de fitotoxidade para incorporação no manejo de doenças no trigo.(AU)

Seed treatment (ST) is an important tool in the management of diseases in the wheat crop, although few products are indicated for this purpose. The research must carry out studies related to the ST effectiveness using different products and the possible phytotoxic effect. The aim of this study was to perform physiological tests on seeds and evaluate the development of two wheat cultivars (BRS Guamirim and TBIO Toruk), submitted to 13 different ST. Germination and vigor were analyzed for each treatment. The treated seeds were also sown to the field, where the field emergence and fresh root and shoot mass were determined. In the germination test, the seeds treated azoxystrobin and Bacillus amyloliquefaciens presented a decrease in the cultivar TBIO Toruk. Vigor analyzes indicated differences between treatments in the two cultivars, and the dimethomorph treatment presented the lowest vigor for TBIO Toruk and azoxystrobin for the BRS Guamirim. The seeds submitted to the Carboxamide A treatment showed seedlings the highest values of fresh root and shoot mass. The results presented allow the selection of products with low or no phytotoxicity for incorporating in wheat disease management.(AU)

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O tratamento de sementes (TS) é uma importante ferramenta no manejo de doenças na cultura do trigo, embora poucos produtos sejam indicados para esse fim. Por isso, a pesquisa deve realizar trabalhos relacionados à efetividade de diferentes produtos no TS e também o possível efeito fitotóxico. Os objetivos deste trabalho foram realizar testes fisiológicos em sementes e avaliar o desenvolvimento de duas cultivares de trigo (BRS Guamirim e TBIO Toruk), submetidas a 13 diferentes tratamentos de sementes. Para cada tratamento foram analisados a germinação e o vigor. As sementes tratadas também foram semeadas a campo, onde se determinou a emergência a campo e massa fresca de raiz e parte aérea. As sementes tratadas com azoxistrobina e Bacillus amyloliquefaciens resultaram em decréscimo na germinação da cultivar TBIO Toruk. Na análise do vigor houve diferença entre os tratamentos testados para as duas cultivares, sendo que houve redução do vigor em sementes tratadas com dimetomorfe para TBIO Toruk e azoxistrobina para a cultivar BRS Guamirim. As sementes submetidas ao tratamento Carboxamida A resultaram em plântulas com maiores valores de massa fresca de raiz e parte aérea. Os resultados apresentados permitem a seleção de produtos com baixa ou ausência de fitotoxidade para incorporação no manejo de doenças no trigo.

Seed treatment (ST) is an important tool in the management of diseases in the wheat crop, although few products are indicated for this purpose. The research must carry out studies related to the ST effectiveness using different products and the possible phytotoxic effect. The aim of this study was to perform physiological tests on seeds and evaluate the development of two wheat cultivars (BRS Guamirim and TBIO Toruk), submitted to 13 different ST. Germination and vigor were analyzed for each treatment. The treated seeds were also sown to the field, where the field emergence and fresh root and shoot mass were determined. In the germination test, the seeds treated azoxystrobin and Bacillus amyloliquefaciens presented a decrease in the cultivar TBIO Toruk. Vigor analyzes indicated differences between treatments in the two cultivars, and the dimethomorph treatment presented the lowest vigor for TBIO Toruk and azoxystrobin for the BRS Guamirim. The seeds submitted to the Carboxamide A treatment showed seedlings the highest values of fresh root and shoot mass. The results presented allow the selection of products with low or no phytotoxicity for incorporating in wheat disease management.

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Anthracnose (Colletotrichum truncatum) is one of the major diseases of the lima bean culture, found in production fields, causing decrease in productivity. The objective of this study was to evaluate the effect of abiotic and biotic inducers applied in lima bean plants to reduce anthracnose severity. Lima bean accessions were used and treated with: the abiotic inducers calcium silicate (Agrosilício Plus) and silicate clay (Rocksil), using the 3 g dose.L-1; the biotic inducer citric biomass extract (Ecolife), at the dose of 3 mL.L-1; and distilled water as control. To evaluate the resistance induction, the results of severity and degree of resistance of fava bean at 7, 11, 15, 19 and 23 days after inoculation were considered according to the scale of grades and classes of reactions. The design was a randomized block in a factorial arrangement 4 × 15 (treatments × hits) with four blocks. Resistance inducers Agrosilicon Plus, Ecolife and Rocksil have potential to be used in the management of anthracnose in fava bean. The studied accesses showed degree of resistance, being able to be explored in relation to obtaining anthracnose resistant cultivars in future breeding programs of this crop.(AU)

A antracnose é uma das principais doenças da cultura do feijão-fava (Phaseolus lunatus L.), sendo encontrada em campos de produção e com grande potencial de causar redução na produtividade. O objetivo do trabalho foi determinar o efeito de indutores abiótico e biótico aplicados em plantas de feijão-fava, a fim de diminuir a severidade da antracnose. Foram utilizados 15 acessos de feijão-fava, tratados com os indutores abióticos: silicato de cálcio (Agrosilício Plus) e argila silicatada (Rocksil), utilizando a dose de 3 g.L-1 para ambos os produtos; e o indutor biótico biomassa cítrica (Ecolife), na dose de 3 mL.L-1. Como testemunha, aplicou-se apenas água destilada. Para avaliar a indução de resistência, foram considerados os resultados de severidade e grau de resistência dos acessos de feijão-fava aos 7, 11, 15, 19 e 23 dias após a inoculação, de acordo com escala de notas e classes de reações. O delineamento utilizado foi em blocos casualizados, em arranjo fatorial simples 4 × 15 (tratamentos × acessos) com quatro blocos. Os indutores de resistência Agrosilício Plus, Ecolife e Rocksil apresentaram potencial para serem utilizados no manejo da antracnose em feijão-fava. Os acessos estudados revelaram grau de resistência, podendo ser explorados quanto à obtenção de cultivares resistentes à antracnose em futuros programas de melhoramento genético dessa cultura.(AU)

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Anthracnose (Colletotrichum truncatum) is one of the major diseases of the lima bean culture, found in production fields, causing decrease in productivity. The objective of this study was to evaluate the effect of abiotic and biotic inducers applied in lima bean plants to reduce anthracnose severity. Lima bean accessions were used and treated with: the abiotic inducers calcium silicate (Agrosilício Plus) and silicate clay (Rocksil), using the 3 g dose.L-1; the biotic inducer citric biomass extract (Ecolife), at the dose of 3 mL.L-1; and distilled water as control. To evaluate the resistance induction, the results of severity and degree of resistance of fava bean at 7, 11, 15, 19 and 23 days after inoculation were considered according to the scale of grades and classes of reactions. The design was a randomized block in a factorial arrangement 4 × 15 (treatments × hits) with four blocks. Resistance inducers Agrosilicon Plus, Ecolife and Rocksil have potential to be used in the management of anthracnose in fava bean. The studied accesses showed degree of resistance, being able to be explored in relation to obtaining anthracnose resistant cultivars in future breeding programs of this crop.(AU)

A antracnose é uma das principais doenças da cultura do feijão-fava (Phaseolus lunatus L.), sendo encontrada em campos de produção e com grande potencial de causar redução na produtividade. O objetivo do trabalho foi determinar o efeito de indutores abiótico e biótico aplicados em plantas de feijão-fava, a fim de diminuir a severidade da antracnose. Foram utilizados 15 acessos de feijão-fava, tratados com os indutores abióticos: silicato de cálcio (Agrosilício Plus) e argila silicatada (Rocksil), utilizando a dose de 3 g.L-1 para ambos os produtos; e o indutor biótico biomassa cítrica (Ecolife), na dose de 3 mL.L-1. Como testemunha, aplicou-se apenas água destilada. Para avaliar a indução de resistência, foram considerados os resultados de severidade e grau de resistência dos acessos de feijão-fava aos 7, 11, 15, 19 e 23 dias após a inoculação, de acordo com escala de notas e classes de reações. O delineamento utilizado foi em blocos casualizados, em arranjo fatorial simples 4 × 15 (tratamentos × acessos) com quatro blocos. Os indutores de resistência Agrosilício Plus, Ecolife e Rocksil apresentaram potencial para serem utilizados no manejo da antracnose em feijão-fava. Os acessos estudados revelaram grau de resistência, podendo ser explorados quanto à obtenção de cultivares resistentes à antracnose em futuros programas de melhoramento genético dessa cultura.(AU)

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Background: Escherichia coli has been widely used as a host to clone and express heterologous genes. However, there are few vectors available for cloning and expressing extremely toxic genes, which limits further basic and applied research on extremely toxic proteins. Results: In this study, a novel vector pAU10 was constructed in E. coli. pAU10 utilizes the combination of the efficient but highly repressible T7-lacO promoter/operator and the strong rrnBT2 transcriptional terminator upstream of the T7 promoter to strictly control unwanted transcription of the extremely toxic gene; in addition, the trp promoter/operator is oriented opposite to the T7 promoter to control the production of the antisense RNA that may block the translation of leaky mRNA. Without the supplementation of IPTG and L-tryptophan in the culture medium, transcription of the extremely toxic gene by the T7 promoter is highly repressed, and the trp promoter produces the antisense RNA, which strictly prevents unwanted expression of the extremely toxic protein in E. coli. With the supplementation of IPTG and L-tryptophan, the T7 promoter efficiently transcribes the extremely toxic gene, and the trp promoter does not produce the antisense RNA, ensuring efficient expression of the extremely toxic protein in E. coli. Tight regulation and efficiency of expression of an extremely toxic gene cloned in the vector pAU10 were confirmed by cloning and expressing the restriction endonuclease-encoding gene bamHI without its corresponding methylase gene in E. coli JM109(DE3). Conclusion: pAU10 is a good vector used for cloning and expressing extremely toxic genes in E. coli.

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Resumen La mayoría de los Errores Innatos del Metabolismo (EIM) no tienen un tratamiento efectivo. Las terapias tradicionales tratan de reducir los sustratos, reemplazar el producto no formado, que puede ser esencial y suplementar con cofactores. También se emplea la activación de vías alternativas para la eliminación de productos intermedios tóxicos, como en el caso de los defectos del ciclo de la urea y para algunas condiciones, se dispone de la terapia de reemplazo enzimático (TRE), del trasplante de células hematopoyéticas y del trasplante hepático. En los últimos años se han desarrollado nuevas estrategias e caces para tratar estas enfermedades. Con esta revisión, se busca explicar de forma sencilla las distintas opciones terapéuticas más recientes, y en algunos casos, tratamientos prometedores para ciertos errores innatos de metabolismo (EIM). En concreto se hará referencia en primer lugar al uso terapéutico de pequeñas moléculas activas, que han surgido en las últimas dos décadas como un enfoque promisorio para el tratamiento de este heterogéneo grupo de trastornos, que incluyen terapia para restauración de la lectura, chaperonas farmacológicas, reguladores de la proteostasis, inhibidores de sustrato e inductores de autofagia. Estas pequeñas moléculas actúan en diferentes niveles celulares, y el conocimiento de los distintos procesos proporciona nuevas herramientas para establecer un tratamiento innovador.

Abstract Most Inborn Errors of Metabolism diseases do not have an effective treatment. Traditional therapies try to reduce substrates, replace non-formed product, which may be essential and supplement with cofactors. Activation of alternative routes for the disposal of toxic intermediates is also employed, as in the case of urea cycle defects for some conditions, enzyme replacement therapy (ERT), Hematopoietic Cell Transplantation and liver transplantation are available. In recent years new effective strategies have been developed to treat these diseases. This review seeks to explain in a simple way the different therapeutic options and, in some cases, promising treatments for certain inborn errors of metabolism (IEM). Specifically, reference will be made first to the therapeutic use of small active molecules, which have emerged in the last two decades as a promising approach for the treatment of this heterogeneous group of disorders, including: read-through therapy, pharmacological chaperones, protease inhibitors, substrate inhibitors and autophagy inducers. These small molecules act on different cellular levels, and the knowledge of the different processes provides new tools to establish an innovative treatment.

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Abstract Introduction: We developed and tested a new system for inducing the healing of diabetic foot ulcers. The system relies on the regenerative properties of its two components: an insole with a sheet of natural latex and a device that contains a matrix of light emitting diodes with wavelength of 635 nm. Methods The electronic and latex based devices were developed, and a four weeks test was performed in one control group (CG) of five ulcers and one experimental group (EG) of eight ulcers. The CG was treated with a standard approach, based on a silver-releasing foam dressing, and the EG was treated with the system under test. For each ulcer, an index for quantifying the percentage ulcer recovery, named CRU(%), has been calculated; a CRU(%) = 0% means no healing, and a CRU(%) = 100% means total healing. Results There were statistically significant increases of CRU(%) of 51.8% (p = 0.022), for the CG, and of 78.4% (p < 0.001), for the EG. The increase in the EG was higher than the increase in the CG, and the difference was statistically significant (p < 0.001). The results showed that the proposed method had, for these particular sets of ulcers, faster healing rates, than for the standard method. Conclusion The results hint that the proposed method seems promising as a future treatment method. However, the technique must undergo further testing before it can be considered for extensive clinical applications.

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PROBLEM: A wide variety of mediators are involved in inflammatory processes. However, the identity of those participating in vaginal immune responses has not been established. We correlated extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-8 (MMP-8), hyaluronan (HA), hyaluronidase-1 (Hyal-1), human ß-defensin-2 (hBD2), and neutrophil gelatinase-associated lipocalin (NGAL) concentrations with the extent of leukocyte infiltration into the vagina and suggest their participation in vaginal inflammation. METHODS OF STUDY: Vaginal fluid was obtained from 233 women seen at the outpatient clinic in the Department of Obstetrics and Gynecology at Campinas University, Brazil. The magnitude of vaginal inflammation was determined by the leukocyte count on vaginal smears and categorized as no inflammation (0 leukocytes/field), moderate inflammation (1-4 leukocytes/field), and intense inflammation (>4 leukocytes/field). Concentrations of EMMPRIN, MMP-8, HA, Hyal-1, hBD2, and NGAL were determined in vaginal fluid by ELISA. RESULTS: EMMPRIN, MMP-8, HA, hBD2, and NGAL concentration increased with elevated leukocyte numbers (P < 0.05), while Hyal-1 did not. EMMPRIN concentrations were correlated with HA and MMP-8 levels. CONCLUSION: EMMPRIN, MMP-8, HA, ß-defensin, and NGAL are elevated in women with vaginal inflammation.

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The effects of deslorelin acetate use in inducing ovulation need to be clarified to improve the results of equine embryo transfer. The mRNA abundance for angiogenic factors and LH receptor (LHR) in corpus luteum (CL) was studied in mares with natural (control group [CG]) and induced ovulation with deslorelin acetate (treatment group [TG]; follicles: ≥ 35 mm). Transrectal ultrasonography was used to verify the ovulation day, and on Days 4, 8, and 12 after ovulation (Day 0), CL samples were obtained through ultrasound-guided biopsy. The messenger RNA expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and LHR genes were analyzed by real-time polymerase chain reaction. A positive correlation was observed between VEGF and LHR (P < 0.00001, r = 0.78), and it was possible to detect higher LHR expression in the TG than in the CG on Day 4 (P < 0.05). Moreover, this expression was higher on Days 4 and 8 than on Day 12 in the TG. Basic fibroblast growth factor was also expressed in luteal tissue on all days for both groups; however, these differences were not significant. In conclusion, deslorelin acetate was effective for the induction of ovulation in mares, resulting in higher expression of LHR, especially on the fourth day after ovulation. In addition, VEGF expression was influenced by induced ovulation, with a lower level on Day 12, which is expected in nonpregnant mares.

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