Palate vault morphology in Down syndrome

Moire topography was used to quantitatively determine the shape of the palatal vault in 57 Spanish patients with Down syndrome (DS) (38 males and 19 females; age range 18-36 years) and in 100 normal controls (N) (76 males and 24 females; age range 20-29 years). The topographic image for each palatal vault was analyzed and approximately 40 sets of coordinates (x, y, z) were recorded. Other parameters, including length, width and maximum height, were recorded from the palate vault images. No appreciable sexual dimorphism in palate dimensions was observed in DS subjects versus the situation in N subjects. Globally, the average N dimensions were significantly greater than those in the DS patients (P < 0.005). A special palatal morphology was found to be associated with DS, with different ratios for the three dimensions (mean factor 0.88 for length, 0.81 for width and 0.73 for height), versus the healthy palatal vaults. It is concluded that palatal morphology in DS fits an elliptic paraboloid. On the other hand, no lineal correlation was observed between height, width and length in the DS and N groups. The scatter plots of bivariate data exhibited a shapeless morphology. The lineal correlation coefficients ranged from 0.008 to 0.33 for the DS and N groups.     

Identification of paraoxonase 3 gene (PON3) missense mutations in a population of southern Italy

PON gene family includes at least three members termed PON1, PON2 and PON3, and it is mapped on human chromosome 7q21-q22. PON1 and PON3 gene products are constituents of high density lipoprotein (HDL) and have many enzymatic properties and antioxidant activity. PONs are proposed to participate in the prevention of low density lipoprotein (LDL) oxidation. PON1 and PON2 genes have missense polymorphisms, but, to date, no missense variants are reported in PON3 gene. In this work we explored the existence of genetic variants within the PON3 coding sequences. Five point mutations were identified by direct sequencing of genomic DNA derived from 250 randomly selected DNA samples of 1143 blood donors living in southern Italy. Three were silent mutations, while two were missense mutations that give rise to amino acid substitutions at positions 311 (S>T) and 324 (G>D). The missense variations in the DNA of the 1143 samples had frequencies of 0.22% (5 out of 2286 alleles) for the S311T mutation, and 0.57% (13 out of 2286 alleles) for the G324D mutation. The effect of these variants on the metabolic activity of paraoxonase 3 remains to be further evaluated.     

Superovulatory response of ovarian follicles of Wave 1 versus Wave 2 in heifers

Experiments were designed to test the hypotheses that ovarian follicular response to superstimulatory treatment initiated during Wave 1 is equivalent to that of Wave 2, and recovery rate and quality of ova embryos derived from follicles of Wave 1 are equivalent to those derived from follicles of Wave 2. In a preliminary experiment (Experiment 1), heifers were given Folltropin-V (20 mg NIH-FSH-P1, im, bid for 5 d) beginning the day after emergence of the first (n=10) or second (n=10) follicular wave of the estrous cycle, equivalent to approximately Day 1 and Day 10, respectively (Day 0=ovulation). Luteolysis was induced with cloprostenol (500 mug im, bid) on the fourth day of treatment. Fewer (P<0.05) ovulations per heifer were induced in the Wave 1 group than in the Wave 2 group (4.6+/-1.0 vs 9.1+/-1.3). However, the interval from wave emergence to initiation of treatment was found, in retrospect, to have been longer (P<0.05) in the Wave 1 group, i.e., treatment was initiated relatively later with respect to wave emergence. Experiment 2 was designed to correct this disparity and to initiate the same treatment protocol on the day of wave emergence rather than the day after (n=21 per Wave group). There was no difference between Wave 1 and Wave 2 groups in the interval from wave emergence to initiation of treatment (0.4+/-0.1 d), the number of ovulations detected by ultrasonography (6.6+/-1.0 vs 8.2+/-1.7), the number of CL detected at slaughter (6.5+/-0.9 vs 8.1+/-1.8), the total number of ova embryos recovered (5.2+/-0.7 vs 5.1+/-0.8), or the number of fertilized embryos collected (2.8+/-0.6 vs 3.0+/-0.6). In addition, there was no difference between groups in the proportion of heifers that ovulated in either experiment; collectively, luteolysis and ovulation was induced in 58 of 60 heifers. The results supported the general hypothesis that follicles and oocytes of the first and second follicular waves are equivalent in the response to superstimulatory treatment. Regardless of which follicular wave, initiation of treatment near the time of wave emergence appears critical for maximal superovulatory response. Because of the consistency in the time of emergence of Wave 1 (day of ovulation) and equivalence in superovulatory response, use of Wave 1 rather than subsequent follicular waves may be more convenient and time-sparing in superovulation programs; the day of estrus (day before ovulation) may be used as a consistent point of reference for the start of treatment.     

Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice

Hyaluronic acid (HA), an essential component of the extracellular matrix, is an efficient space filler that maintains hydration, serves as a substrate for assembly of proteoglycans and is involved in wound healing. Although numerous pieces of evidence demonstrate beneficial effects in promoting wound healing in diabetes, a systemic approach has never been tested. We used an incisional wound healing model in genetically diabetic mice to test the effects of systemic injection of HA. Diabetic (n = 56) and normoglycemic (n = 56) mice were subjected to incision and randomized (8 groups of 7 animals each) to receive HA at different doses, 7.5, 15 and 30 mg/kg/i.p., or vehicle (0.9% NaCl solution) for 12 days. At the end of the experiment animals were sacrificed and skin wounds were excised for histological, biochemical and molecular analysis. Histology revealed that the most effective dose to improve wound repair and angiogenesis in diabetic mice was 30 mg/kg. Furthermore HA injection (30 mg/kg) improved the altered healing pattern in diabetic animals, increased skin remodeling proteins TGF-β and transglutaminase-II and restored the altered expression of cyclin B1/Cdc2 complex. Evaluation of skin from diabetic animals injected with HA revealed also an increase in HA content, suggesting that systemic injection may be able to restore the reduced intracellular HA pool of diabetic mice. Finally HA markedly improved skin mechanical properties. These promising results, if confirmed in a clinical setting, may improve the care and management of diabetic patients.     

Temporal variations in the diet of pearly razorfish Xyrichtys novacula (Osteichthyes: Labridae)

The diet of pearly razorfish Xyrichtys novacula, caught monthly along the shores of the Island of Lampedusa, appeared to be mainly composed of crustaceans, followed by colonial ascidians, molluscs and polychaetes. Among prey, sand dwellers and phanerogam‐associated species were recorded. In winter months, the diet was characterized by a small number of prey items, dominated by colonial ascidians, while in spring and summer a wider prey array was recorded. Dietary indices show that X. novacula do not strictly exploit benthic prey but also pelagic organisms, such as copepods. This feeding behaviour reached its peak in March and October, when the abundance of primary consumers was at its highest after phytoplankton blooms. Furthermore, X. novacula caught prey organisms according to their availability and seasonal patterns during their life cycles, irrespective of fish size.     

Genotypic Analyses of Shiga Toxin-Producing Escherichia coli O157 and Non-O157 Recovered from Feces of Domestic Animals on Rural Farms in Mexico

Shiga toxin-producing Escherichia coli (STEC) are zoonotic enteric pathogens associated with human gastroenteritis worldwide. Cattle and small ruminants are important animal reservoirs of STEC. The present study investigated animal reservoirs for STEC in small rural farms in the Culiacan Valley, an important agricultural region located in Northwest Mexico. A total of 240 fecal samples from domestic animals were collected from five sampling sites in the Culiacan Valley and were subjected to an enrichment protocol followed by either direct plating or immunomagnetic separation before plating on selective media. Serotype O157:H7 isolates with the virulence genes stx2, eae, and ehxA were identified in 40% (26/65) of the recovered isolates from cattle, sheep and chicken feces. Pulse-field gel electrophoresis (PFGE) analysis grouped most O157:H7 isolates into two clusters with 98.6% homology. The use of multiple-locus variable-number tandem repeat analysis (MLVA) differentiated isolates that were indistinguishable by PFGE. Analysis of the allelic diversity of MLVA loci suggested that the O157:H7 isolates from this region were highly related. In contrast to O157:H7 isolates, a greater genotypic diversity was observed in the non-O157 isolates, resulting in 23 PFGE types and 14 MLVA types. The relevant non-O157 serotypes O8:H19, O75:H8, O111:H8 and O146:H21 represented 35.4% (23/65) of the recovered isolates. In particular, 18.5% (12/65) of all the isolates were serotype O75:H8, which was the most variable serotype by both PFGE and MLVA. The non-O157 isolates were predominantly recovered from sheep and were identified to harbor either one or two stx genes. Most non-O157 isolates were ehxA-positive (86.5%, 32/37) but only 10.8% (4/37) harbored eae. These findings indicate that zoonotic STEC with genotypes associated with human illness are present in animals on small farms within rural communities in the Culiacan Valley and emphasize the need for the development of control measures to decrease risks associated with zoonotic STEC.     

Successful colon cancer eradication after chemoimmunotherapy is associated with profound phenotypic change of intratumoral myeloid cells

IL-12 is a potent immunostimulatory cytokine, but its impact as an antitumor drug in clinical practice is limited. Upsurge of regulatory T cells (Treg) in the tumor milieu has been proposed to limit the efficacy of the treatment. In this paper, two drugs (cyclophosphamide [CPA] and anti-CD25 mAb) widely used to eliminate Treg were used in an attempt to enhance the antitumor effect of IL-12 gene therapy. Both anti-CD25 and CPA combined with IL-12 were able to deplete intratumoral Treg and myeloid-derived suppressor cells (MDSC), but only IL-12 plus CPA achieved significant antitumor activity in mice with large established s.c. colon carcinoma. This therapeutic effect was associated with the emergence of a heterogeneous population of myeloid cells within the tumor, termed inflammatory myeloid cells (IMC), composed of Ly6C(high)Ly6G(low) inflammatory monocytes and Ly6G(high)Ly6C(+) neutrophils. IMC showed a distinctive pattern of cytokine/chemokine production, and in contrast to MDSC, they did not induce conversion of naive CD4(+) T cells into Treg. The appearance of IMC coincided with intense tumor infiltration by effector T cells, which was abrogated by elimination of IMC by anti-Gr1 mAb, a maneuver that abolished the antitumor effect of the therapy. Therefore, the combination of IL-12 and CPA eliminates intratumoral Treg and MDSC, while it induces the appearance of IMC within the tumor microenvironment. The latter effect is essential to facilitate effector T cell infiltration and subsequent tumor elimination.     

Is Cassava the Answer to African Climate Change Adaptation?

This paper examines the impacts of climate change on cassava production in Africa, and questions whether cassava can play an important role in climate change adaptation. First, we examine the impacts that climate change will likely have on cassava itself, and on other important staple food crops for Africa including maize, millets, sorghum, banana, and beans based on projections to 2030. Results indicate that cassava is actually positively impacted in many areas of Africa, with ?3.7% to +17.5% changes in climate suitability across the continent. Conversely, for other major food staples, we found that they are all projected to experience negative impacts, with the greatest impacts for beans (?16%?±?8.8), potato (?14.7?±?8.2), banana (?2.5%?±?4.9), and sorghum (?2.66%?±?6.45). We then examined the likely challenges that cassava will face from pests and diseases through the use of ecological niche modeling for cassava mosaic disease, whitefly, brown streak disease and cassava mealybug. The findings show that the geographic distribution of these pests and diseases are projected to change, with both new areas opening up and areas where the pests and diseases are likely to leave or reduce in pressure. We finish the paper by looking at the abiotic traits of priority for crop adaptation for a 2030 world, showing that greater drought tolerance could bring some benefits in all areas of Africa, and that cold tolerance in Southern Africa will continue to be a constraint for cassava despite a warmer 2030 world, hence breeding needs to keep a focus on this trait. Importantly, heat tolerance was not found to be a major priority for crop improvement in cassava in the whole of Africa, but only in localized pockets of West Africa and the Sahel. The paper concludes that cassava is potentially highly resilient to future climatic changes and could provide Africa with options for adaptation whilst other major food staples face challenges.     

Quality Control Test for Sequence-Phenotype Assignments

Relating a gene mutation to a phenotype is a common task in different disciplines such as protein biochemistry. In this endeavour, it is common to find false relationships arising from mutations introduced by cells that may be depurated using a phenotypic assay; yet, such phenotypic assays may introduce additional false relationships arising from experimental errors. Here we introduce the use of high-throughput DNA sequencers and statistical analysis aimed to identify incorrect DNA sequence-phenotype assignments and observed that 10–20% of these false assignments are expected in large screenings aimed to identify critical residues for protein function. We further show that this level of incorrect DNA sequence-phenotype assignments may significantly alter our understanding about the structure-function relationship of proteins. We have made available an implementation of our method at http://bis.ifc.unam.mx/en/software/chispas.