Mutations in dynein link motor neuron degeneration to defects in retrograde transport

Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology. These mutations exclusively perturb neuron-specific functions of dynein.     

Tanjungides A and B: New Antitumoral Bromoindole Derived Compounds from Diazona cf formosa. Isolation and Total Synthesis

Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D and 2D NMR. The stereochemistry of the cyclised cystine present in both compounds was determined by Marfey’s analysis after chemical degradation and hydrolysis. We also report the first total synthesis of these compounds using methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11 chemical steps. Tanjungides A and B exhibit significant cytotoxicity against human tumor cell lines.     

Effect of nanoclay incorporation method on mechanical and water vapor barrier properties of starch-based films

The objective of this study was to investigate the influence of nanoclay incorporation procedure on the mechanical and water vapor barrier properties of starch/nanoclay composite films. Cassava starch films were prepared with (nanocomposite) and without nanoclay (control) in two steps: firstly the production of extruded pellets and secondly thermo-pressing. The nanocomposite films were prepared via two different methods: in D samples the nanoclay was dispersed in glycerol and subsequently incorporated into the starch; and in ND samples all ingredients were added in a single step before the extrusion. All the composite-films were prepared with cassava starch using 0.25 g of glycerol/g of starch and 0.03 g of nanoclay/g of starch. Control samples showed V_A-type crystallinity induced by the manufacturing process and the nanocomposites presented a semicrystalline and intercalated structure. The nanoclay improved the water vapor barrier properties of the starch film and this effect was more pronounced in D samples, where the water vapor permeability (K^w) was 60% lower than that of the control samples. The K^w reduction was associated with decreases in the effective diffusion coefficient (approximately 61%) and in the coefficient of solubility (approximately 22-32%). On the other hand, the incorporation of nanoclay increased the tensile strength and the rigidity of the films and this effect was more significant when the nanoclay was dispersed in glycerol. Thus, the incorporation of nanoclay into starch-based films is a promising way to manufacture films with better mechanical and water vapor barrier properties.     

<Emphasis Type="Italic">Lupinus albus</Emphasis> Conglutin Gamma Modifies the Gene Expressions of Enzymes Involved in Glucose Hepatic Production <Emphasis Type="Italic">In Vivo</Emphasis>

Lupinus albus seeds contain conglutin gamma (Cγ) protein, which exerts a hypoglycemic effect and positively modifies proteins involved in glucose homeostasis. Cγ could potentially be used to manage patients with impaired glucose metabolism, but there remains a need to evaluate its effects on hepatic glucose production. The present study aimed to analyze G6pc, Fbp1, and Pck1 gene expressions in two experimental animal models of impaired glucose metabolism. We also evaluated hepatic and renal tissue integrity following Cγ treatment. To generate an insulin resistance model, male Wistar rats were provided 30% sucrose solution ad libitum for 20 weeks. To generate a type 2 diabetes model (STZ), five-day-old rats were intraperitoneally injected with streptozotocin (150 mg/kg). Each animal model was randomized into three subgroups that received the following oral treatments daily for one week: 0.9% w/v NaCl (vehicle; IR-Ctrl and STZ-Ctrl); metformin 300 mg/kg (IR-Met and STZ-Met); and Cγ 150 mg/kg (IR-Cγ and STZ-Cγ). Biochemical parameters were assessed pre- and post-treatment using colorimetric or enzymatic methods. We also performed histological analysis of hepatic and renal tissue. G6pc, Fbp1, and Pck1 gene expressions were quantified using real-time PCR. No histological changes were observed in any group. Post-treatment G6pc gene expression was decreased in the IR-Cγ and STZ-Cγ groups. Post-treatment Fbp1 and Pck1 gene expressions were reduced in the IR-Cγ group but increased in STZ-Cγ animals. Overall, these findings suggest that Cγ is involved in reducing hepatic glucose production, mainly through G6pc inhibition in impaired glucose metabolism disorders.     

Chemical and Nutritional Composition of Tejate, a Traditional Maize and Cacao Beverage from the Central Valleys of Oaxaca, Mexico

Foam-topped cacao and maize beverages have a long history in Mesoamerica. Tejate is such a beverage found primarily in the Zapotec region of the Central Valleys of Oaxaca, Mexico. Historically tejate has been ceremonially important but also as an essential staple, especially during periods of hard fieldwork. However, the nutritional contribution of traditional foods such as tejate has not been investigated. We analyzed tejate samples from three Central Valley communities, vendors in urban Oaxaca markets and one migrant vendor in California, USA for their proximate composition, amino acid content and scores, and mineral and methylxanthine content. Nutritional and chemical variation exists among tejate recipes, however, the beverage is a source of energy, fat, methylxanthines, K, Fe and other minerals although their availability due to presence of phytates remains to be determined. Tejate is a source of protein comparable to an equal serving size of tortillas, with protein quality similarly limited in both. Tejate provides the nutritional benefits of maize, and some additional ones, in a form appealing during hot periods of intense work, and year round because of its cultural significance. Its substitution by sodas and other high glycemic beverages may have negative nutritional, health and cultural consequences.     

Production of Hyaluronic Acid by Streptococcus zooepidemicus on Protein Substrates Obtained from Scyliorhinus canicula Discards

This work investigates the production of hyaluronic acid (H) by Streptococcus equi subsp. zooepidemicus in complex media formulated with peptones obtained from Scyliorhinus canicula viscera by-products. Initially, in batch cultures, the greatest productions were achieved using commercial media (3.03 g/L) followed by peptones from alcalase hydrolyzed viscera (2.32 g/L) and peptones from non-hydrolyzed viscera (2.26 g/L). An increase of between 12% and 15% was found in subsequent fed-batch cultures performed on waste peptones. Such organic nitrogen sources were shown to be an excellent low-cost substrate for microbial H, saving more than 50% of the nutrient costs.     

Diterpenes from Salvia broussonetii transformed roots and their insecticidal activity

The new diterpenes brussonol (1) and iguestol (6alpha,11-dihydroxy-12-methoxy-abieta-8,11,13-triene) (2) with an icetexane and a dehydroabietane skeleton, respectively, have been isolated from hairy root cultures of Salvia broussonetii. Other previously known diterpenes, 7-oxodehydroabietane, 11-hydroxy-12-methoxyabietatriene, taxodione, inuroyleanol, ferruginol, deoxocarnosol 12-methyl ether, cryptojaponol, pisiferal, sugiol, isomanool, 14-deoxycoleon U, 6alpha-hydroxydemethylcryptojaponol, demethylsalvicanol, and demethylcryptojaponol, were also obtained from these roots. The insect antifeedant and toxic effects of several of these compounds were investigated against the insect pests Spodoptera littoralis and Leptinotarsa decemlineata. Additionally, their comparative cytotoxic effects were tested on insect Sf9 and mammalian CHO cells. Demethylsalvicanol (4) was a moderate antifeedant to L. decemlineata, whereas brussonol (1) was inactive. 14-Deoxycoleon U (15) was the strongest antifeedant, whereas demethylcryptojaponol (11) was toxic to this insect. None of these compounds had antifeedant or negative effects on S. littoralis ingestion or weight gains after oral administration. Demethylcryptojaponol (11) was cytotoxic to mammalian CHO and insect Sf9 cell lines, followed by the icetexane derivative brussonol (1), with moderate cytotoxicity in both cases. The remainder of the test compounds showed a strong selective cytotoxicty to insect Sf9 cells, with demethylsalvicanol (4) being the most active.     

Phenotypic and Genetic Diversity in Strains of Common Blight Bacteria (Xanthomonas campestris pv. phaseoli and X. campestris pv. phaseoli var. fuscans) in a Secondary Center of Diversity of the Common Bean Host Suggests Multiple Introduction Events

ABSTRACT Common bacterial blight (CBB) disease of the common bean (Phaseolus vulgaris) is caused by Xanthomonas campestris pv. phaseoli and the brown-pigmented variant X. campestris pv. phaseoli var. fuscans. CBB first was described in Castilla y León County, Spain, in 1940, and is now a major constraint on common bean production. In this secondary center of diversity of the common bean, large-seeded Andean cultivars predominate, although medium-seeded Middle American cultivars also are grown. Xanthomonad-like bacteria associated with CBB in Castilla y León were characterized on the basis of carbohydrate metabolism, brown pigment production, genetic analyses (repetitive-element polymerase chain reaction [rep-PCR] and random amplified polymorphic DNA [RAPD]) and pathogenicity on cultivars representing the two common bean gene pools (Andean and Middle American). X. campestris pv. phaseoli was more prevalent (80%) than X. campestris pv. phaseoli var. fuscans (20%). Patterns of carbohydrate metabolism of Spanish CBB bacteria were similar to those of known strains; and only X. campestris pv. phaseoli var. fuscans strains utilized mannitol as a sole carbon source. rep-PCR and RAPD analyses revealed relatively little genetic diversity among Spanish X. campestris pv. phaseoli strains, and these strains were placed together with New World strains into a large cluster. Similar to other New World strains, representative Spanish X. campestris pv. phaseoli strains were highly pathogenic on bean cultivars of both gene pools, showing no gene pool specialization such as that found in certain East African strains. Genetic analyses and pathogenicity tests confirmed and extended previous results, indicating that these East African strains represent distinct xanthomonads that independently evolved to be pathogenic on common bean. X. campestris pv. phaseoli var. fuscans strains were more closely related and genetically distinct from X. campestris pv. phaseoli strains. However, two distinct clusters of X. campestris pv. phaseoli var. fuscans strains were identified, one having the most New World strains and the other having the most African strains. Spanish strains were placed in both clusters, but all strains tested were highly pathogenic on bean cultivars of both gene pools. Together, our results are consistent with multiple introductions of CBB bacteria into Spain. These findings are discussed in terms of breeding for CBB resistance and the overall understanding of the genetic diversity and evolution of CBB bacteria.     

Drought-induced oxidative stress in Canarian laurel forest tree species growing under controlled conditions

We studied photoprotection and antioxidative protection in the three major species of the Canarian laurel forest (Laurus azorica (Seub.) Franco, Persea indica (L.) K. Spreng and Myrica faya Aiton). Trees were exposed to drought under controlled conditions by withholding water until leaf relative water content (RWC) reached 50-55%. Drought reduced photosynthetic rate (P(N)) and was associated with decreased quantum yield of photosystem II (PSII) electron transport and increased non-photochemical quenching (NPQ) in L. azorica and M. faya, but did not increase NPQ in P. indica. Drought-treated trees of L. azorica had the highest de-epoxidation state (DPS) of the xanthophyll cycle and the highest zeaxanthin (Z) concentration, suggesting that this species had more effective photoprotective mechanisms than M. faya and P. indica. Moreover, beta-carotene remained unaltered in L. azorica trees during drought, suggesting that the chloroplasts of this species are better protected against oxidative stress than those of M. faya and P. indica. Increased antioxidation by ascorbate peroxidase, superoxide dismutase and glutathione reductase in L. azorica removed activated oxygen species (AOS) generated during drought treatment. Although M. faya was able to increase its energy dissipation rate by forming Z and thus increasing the DPS of the xanthophyll cycle, it did not respond to drought-induced oxidative stress with the result that beta-carotene degradation occurred. Persea indica did not activate an energy dissipation mechanism in response to drought treatment, hence formation of AOS was likely high in the drought-treated trees. In general, L. azorica was most resistant and P. indica most sensitive to photoinhibition and oxidative stress during drought.