A mutation in caspase-9 decreases the expression of BAFFR and ICOS in patients with immunodeficiency and lymphoproliferation

Lymphocyte apoptosis is mainly induced by either death receptor-dependent activation of caspase-8 or mitochondria-dependent activation of caspase-9. Mutations in caspase-8 lead to autoimmunity/lymphoproliferation and immunodeficiency. This work describes a heterozygous H237P mutation in caspase-9 that can lead to similar disorders. H237P mutation was detected in two patients: Pt1 with autoimmunity/lymphoproliferation, severe hypogammaglobulinemia and Pt2 with mild hypogammaglobulinemia and Burkitt lymphoma. Their lymphocytes displayed defective caspase-9 activity and decreased apoptotic and activation responses. Transfection experiments showed that mutant caspase-9 display defective enzyme and proapoptotic activities and a dominant-negative effect on wild-type caspase-9. Ex vivo analysis of the patients' lymphocytes and in vitro transfection experiments showed that the expression of mutant caspase-9 correlated with a downregulation of BAFFR (B-cell-activating factor belonging to the TNF family (BAFF) receptor) in B cells and ICOS (inducible T-cell costimulator) in T cells. Both patients carried a second inherited heterozygous mutation missing in the relatives carrying H237P: Pt1 in the transmembrane activator and CAML interactor (TACI) gene (S144X) and Pt2 in the perforin (PRF1) gene (N252S). Both mutations have been previously associated with immunodeficiencies in homozygosis or compound heterozygosis. Taken together, these data suggest that caspase-9 mutations may predispose to immunodeficiency by cooperating with other genetic factors, possibly by downregulating the expression of BAFFR and ICO

Variation of Vitamin D in cow’s milk and interaction with β-lactoglobulin

Vitamin D is the collective name for a group of closely related lipids, whose main biological function is to maintain serum calcium and phosphorus concentrations within the normal range by enhancing the efficiency of the small intestine to absorb these minerals from the diet. We used a commercially available ELISA method for the determination of vitamin D in bovine milk. Individual milk samples from two different Italian Friesian herds were analysed. The enzyme immunoassay method used was confirmed as a useful tool to measure the vitamin D in the milk as it greatly reduces the time required to perform the conventional HPLC analysis. An interesting variation was found among individual animals that may be associated with management factors and specific genetic effects. A relationship was highlighted between vitamin D and the genetic polymorphism of β-lactoglobulin, the main bovine whey protein which is involved in the transport of small hydrophobic molecules such as retinol and vitamin D. The relatively high content of vitamin D in most milk samples suggests an opportunity to improve the natural content of vitamin D in milk either by acting on the herd management or selecting individuals genetically predisposed to produce milk with a higher vitamin D content

Different sources of omega-3 polyunsaturated fatty acids affects apparent digestibility, tissue deposition, and tissue oxidative stability in growing female rats

Background Numerous health benefits associated with increased omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption has lead to an increasing variety of available n-3 PUFA sources. However, sources differ in the type, amount, and structural form of the n-3 PUFAs. Therefore, the objective of this study was to determine the effect of different sources of ω-3 PUFAs on digestibility, tissue deposition, eicosanoid metabolism, and oxidative stability. Methods Female Sprague-Dawley rats (age 28 d) were randomly assigned (n = 10/group) to be fed a high fat 12% (wt) diet consisting of either corn oil (CO) or n-3 PUFA rich flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) oil for 8 weeks. Rats were individually housed in metabolic cages to determine fatty acid digestibility. Diet and tissue fatty acid composition was analyzed by gas chromatography and lipid classes using thin layer chromatography. Eicosanoid metabolism was determined by measuring urinary metabolites of 2-series prostaglandins (PGs) and thromoboxanes (TXBs) using enzyme immunoassays. Oxidative stability was assessed by measuring thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) using colorimetric assays. Gene expression of antioxidant defense enzymes was determined by real time quantitative polymerase chain reaction (RT-qPCR). Results Rats fed KO had significantly lower DHA digestibility and brain DHA incorporation than SO and TO-fed rats. Of the n-3 PUFA sources, rats fed SO and TO had the highest n-3 PUFAs digestibility and in turn, tissue accretion. Higher tissue n-3 LC-PUFAs had no significant effect on 2-series PG and TXB metabolites. Despite higher tissue n-3 LC-PUFA deposition, there was no increase in oxidation susceptibility indicated by no significant increase in TBARS or decrease in TAC and gene expression of antioxidant defense enzymes, in SO or TO-fed rats. Conclusions On the basis that the optimal n-3 PUFA sources should provide high digestibility and efficient tissue incorporation with the least tissue lipid peroxidation, TO and SO appeared to be the most beneficial of the n-3 PUFAs sources evaluated in this study

Design and Fabrication of Forged Ti-6Al-4V Blocks with Synthetic Ti-N Inclusions for Estimation of Detectability by Ultrasonic Signal-To-Noise

In the work described subsequently, synthetic “hard alpha” inclusions have been fabricated within Ti-6A1-4V (Ti64) forgings. Several compositions of synthetic hard alpha were made by arc melting Ti sponge and TiN powder. Small solid cylinders of the titanium-nitrogen alloys were made by electro-discharge machining (e. d. m.) the arc-melted ingots to diameters of 0.031, 0.047, 0.062, and 0.078 inches, respectively, with heights equal to the respective diameter. Sets of eight or sixteen each identical cylinders were hot isostatic press (HIP) bonded within forged Ti64 blocks to yield uncracked inclusions with sharp interfaces with the Ti64 matrix. Detectability of the uncracked hard alpha was estimated as a function of flaw size, orientation, and nitrogen content from ultrasonic signal to noise ratios determined from C-Scan images of the blocks. Relationships of detectability to physical properties of hard alpha, and methodologies of signal to noise determinations are discussed

The Garfagnina goat: A zootechnical overview of a local dairy population

Domestic livestock with a limited distribution are increasingly recognized in the action plans of the European Union as a reason for protecting rural land. The preservation and enhancement of the native germplasm and traits selected through the ages in different areas of farming is the first step in increasing typical products at a time when high quality products are increasingly in demand. This is the first time that a zootechnical overview has been performed on the Italian native goat population named "Garfagnina", which is registered on the Tuscan regional repertory of genetic resources at risk of extinction. The aim of the study was to give added value to this population by focusing on particular traits that could be used for promoting typical products. Data on the size of the local goats, zoometric measures, breeding system, milk quality, and genetic polymorphisms were collected to get insight into the current state of the population of this type of goat. The native goat population is reared in Tuscany in central Italy, mostly for its milk. The local goat farms considered in our study are located in the hills and mountains of the northwestern Tuscan Apennine area. For every farm we measured at least 10% of the reproductive females (273), randomly chosen, and all reproductive males (47) for a total of 320 subjects. Regarding the management of the animals and the feeding system, semi-extensive farming is practiced in all the flocks. From a morphological point of view the animals are relatively homogeneous, especially in terms of zoometric data, whereas they show a wider variability regarding coat. Milk gross and fatty acid composition were similar to that reported in the literature for bulk goat milk. Moreover, the average of somatic cell count and standard plate count found in Garfagnina goat milk indicated good hygienic farm management and correct milking practices, although milking is mainly manual. The average number of globules per milliliter found in Garfagnina goat milk was almost double compared with the literature, whereas the average diameter was lower. Milk coagulation properties were scarce, thus indicating poor cheesemaking aptitude of Garfagnina milk. Selecting haplotypes carrying alleles associated with a higher expression of the specific casein could help improve milk cheesemaking aptitude. Moreover, the rather high frequency of the faint CSN1S1*F allele and the occurrence of CSN2*0 might suggest that Garfagnina goat milk could be used, after an appropriate selection, for direct consumption of milk at low casein content for intolerant human subjects

Diversidade de Scarabaeinae (Coleoptera, Scarabaeidae) em mata de galeria no Distrito Federal.

Os coleópteros pertencentes a subfamília Scarabaeinae são popularmente conhecidos como besouros rola-bosta, devido ao hábito de manipular fezes para alimentação e construção dos seus ninhos. Apesar de ser considerado um grupo relativamente bem estudado, pouco se conhece a respeito das espécies que habitam áreas de mata de galeria na região do Cerrado. No entanto, sabe-se que a cobertura florestal representa um elemento determinante da estrutura e diversidade da fauna destes besouros e que as matas de galeria no Cerrado podem ter influências de outros biomas, como a Amazônia e Mata Atlântica. O estudo teve como objetivo avaliar a diversidade de Scarabaeinae em um fragmento de mata de galeria localizado na Fazenda Experimental Água Limpa da Universidade de Brasília (FAL), Brasília, DF. Foram utilizadas 15 armadilhas do tipo pitfall iscadas com carne de porco, moela de frango e fezes humanas, distribuídas em cinco pontos, a uma distância de 15 metros entre si; além de uma armadilha de interceptação de voo. As iscas foram repostas e os besouros coletados semanalmente, durante quatro meses (novembro de 2013 a março de 2014). Foram coletados 2.643 espécimes e 21 espécies, distribuídas em 9 gêneros: Anomiopus, Canthidium, Coprophanaeus, Delthochilum, Dichotomius, Eurysternus, Eutrichillum, Onthophagus e Phanaeus. O gênero Dichotomius foi o que apresentou maior riqueza (6 espécies) e também a maior abundância (1.399 indivíduos). As espécies Dichotomius (Selenocopris) quadraticeps (429 indivíduos) e D. (Selenocopris) bicuspis (309 indivíduos), que obrigatoriamente ocorrem em ambientes florestais, e uma espécie de D. (Luederwaldtinia) do grupo assifer, predominante em áreas de Mata Atlântica, foram as três mais abundantes do gênero. Ambas foram atraídas pelas três iscas, enquanto D. depressicoliis apenas por fezes. Armadilhas do tipo pitfall mostraram-se mais eficientes na coleta de rola-bostas, entretanto, o gênero Anomiopus foi capturado apenas na interceptação de voo

Sr-containing mesoporous bioactive glasses bio-functionalized with recombinant ICOS-Fc: An in vitro study

Osteoporotic bone fractures represent a critical clinical issue and require personalized and specific treatments in order to stimulate compromised bone tissue regeneration. In this clinical context, the development of smart nano-biomaterials able to synergistically combine chemical and biological cues to exert specific therapeutic effects (i.e., pro-osteogenic, anti-clastogenic) can allow the design of effective medical solutions. With this aim, in this work, strontium-containing mesoporous bioactive glasses (MBGs) were bio-functionalized with ICOS-Fc, a molecule able to reversibly inhibit osteoclast activity by binding the respective ligand (ICOS-L) and to induce a decrease of bone resorption activity. N2 adsorption analysis and FT-IR spectroscopy were used to assess the successful grafting of ICOS-Fc on the surface of Sr-containing MBGs, which were also proved to retain the peculiar ability to release osteogenic strontium ions and an excellent bioactivity after functionalization. An ELISA-like assay allowed to confirm that grafted ICOS-Fc molecules were able to bind ICOS-L (the ICOS binding ligand) and to investigate the stability of the amide binding to hydrolysis in aqueous environment up to 21 days. In analogy to the free form of the molecule, the inhibitory effect of grafted ICOS-Fc on cell migratory activity was demonstrated by using ICOSL positive cell lines and the ability to inhibit osteoclast differentiation and function was confirmed by monitoring the differentiation of monocyte-derived osteoclasts (MDOCs), which revealed a strong inhibitory effect, also proven by the downregulation of osteoclast differentiation genes. The obtained results showed that the combination of ICOS-Fc with the intrinsic properties of Sr-containing MBGs represents a very promising approach to design personalized solutions for patients affected by compromised bone remodeling (i.e., osteoporosis fractures)

The 21Na(p,gamma)22Mg Reaction and Oxygen-Neon Novae

The 21Na(p,gamma)22Mg reaction is expected to play an important role in the nucleosynthesis of 22Na in Oxygen-Neon novae. The decay of 22Na leads to the emission of a characteristic 1.275 MeV gamma-ray line. This report provides the first direct measurement of the rate of this reaction using a radioactive 21Na beam, and discusses its astrophysical implications. The energy of the important state was measured to be E$_{c.m.}$= 205.7 $\pm$ 0.5 keV with a resonance strength $\omega\gamma = 1.03\pm0.16_{stat}\pm0.14_{sys}$ meV.Comment: Accepted for publication in Physical Review Letter