Research of the Influence on the Modification of Beryllium in Al–Si Alloy

Modification of molten metal is performed for the eutectic and subeutectic silumins prior to its casting by using strontium, which has a time-limited effect up to 1–1.5 hours. Beryllium is used in order to prolong the modifying effect. The aim of the experiment is to examine both the distribution and the effect of beryllium in the structure on the temporary extension of the modification in the Al–Si alloys in combination with strontium modifier.Перед отливкой расплавленного металла выполняется модифицирование эвтектических и субэвтектических силуминов с помощью стронция, который имеет ограниченный 1–1,5 часами временный эффект воздействия. Бериллий используется для продления модифицирующего эффекта. Целью эксперимента является изучение распределения и влияния бериллия в структуре на временное продление модифицирующего воздействия в сплавах Al–Si в сочетании со стронциевым модификатором.Перед відливанням розтопленого металу виконується модифікування евтектичних і субевтектичних силумінів за допомогою Стронцію, який має обмежений 1–1,5 годинами тимчасовий ефект дії. Берилій використовується для продовження модифікувального ефекту. Метою експерименту є вивчення розподілу та впливу берилію в структурі на тимчасове подовження модифікувальної дії в стопах Al–Si у поєднанні зі стронційовим модифікатором

Bifidobacterium canis sp. Nov., a novel member of the bifidobacterium pseudolongum phylogenetic group isolated from faeces of a dog (canis lupus f. familiaris)

A fructose-6-phosphate phosphoketolase-positive strain (GSD1FST) was isolated from a faecal sample of a 3 weeks old German Shepherd dog. The closest related taxa to isolate GSD1FST based on results from the EZBioCloud database were Bifidobacte-rium animalis subsp. animalis ATCC 25527T, Bifidobacterium animalis subsp. lactis DSM 10140T and Bifidobacterium anseris LMG 30189T, belonging to the Bifidobacterium pseudolongum phylogenetic group. The resulting 16S rRNA gene identities (compared length of 1454 nucleotides) towards these taxa were 97.30, 97.23 and 97.09 %, respectively. The pairwise similarities of strain GSD1FST using argS, atpA, fusA, hsp60, pyrG, rpsC, thrS and xfp gene fragments to all valid representatives of the B. pseudo-longum phylogenetic group were in the concatenated range of 83.08–88.34 %. Phylogenomic analysis based on whole-genome methods such as average nucleotide identity revealed that bifidobacterial strain GSD1FST exhibits close phylogenetic relatedness (88.17 %) to Bifidobacetrium cuniculi LMG 10738T. Genotypic characteristics and phylogenetic analyses based on nine molecular markers, as well as genomic and comparative phenotypic analyses, clearly proved that the evaluated strain should be considered as representing a novel species within the B. pseudolongum phylogenetic group named as Bifidobacterium canis sp. nov. (GSD1FST=DSM 105923T=LMG 30345T=CCM 8806T)

Dysregulation of epicardial adipose tissue in cachexia due to heart failure. the role of natriuretic peptides and cardiolipin

Background: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods: The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = −0.94; P = 0.036). Conclusions: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and ‘healthy’ EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia

Biopolymer-based structuring of liquid oil into soft solids and oleogels using water-continuous emulsions as templates

Physical trapping of a hydrophobic liquid oil in a matrix of water-soluble biopolymers was achieved using a facile two-step process by first formulating a surfactant-free oil-in-water emulsion stabilized by biopolymers (a protein and a polysaccharide) followed by complete removal of the water phase (by either high- or low-temperature drying of the emulsion) resulting in structured solid systems containing a high concentration of liquid oil (above 97 wt %). The microstructure of these systems was revealed by confocal and cryo-scanning electron microscopy, and the effect of biopolymer concentrations on the consistency of emulsions as well as the dried product was evaluated using a combination of small-amplitude oscillatory shear rheometry and large deformation fracture studies. The oleogel prepared by shearing the dried product showed a high gel strength as well as a certain degree of thixotropic recovery even at high temperatures. Moreover, the reversibility of the process was demonstrated by shearing the dried product in the presence of water to obtain reconstituted emulsions with rheological properties comparable to those of the fresh emulsion

pUL21 is a viral phosphatase adaptor that promotes herpes simplex virus replication and spread.

The herpes simplex virus (HSV)-1 protein pUL21 is essential for efficient virus replication and dissemination. While pUL21 has been shown to promote multiple steps of virus assembly and spread, the molecular basis of its function remained unclear. Here we identify that pUL21 is a virus-encoded adaptor of protein phosphatase 1 (PP1). pUL21 directs the dephosphorylation of cellular and virus proteins, including components of the viral nuclear egress complex, and we define a conserved non-canonical linear motif in pUL21 that is essential for PP1 recruitment. In vitro evolution experiments reveal that pUL21 antagonises the activity of the virus-encoded kinase pUS3, with growth and spread of pUL21 PP1-binding mutant viruses being restored in adapted strains where pUS3 activity is disrupted. This study shows that virus-directed phosphatase activity is essential for efficient herpesvirus assembly and spread, highlighting the fine balance between kinase and phosphatase activity required for optimal virus replication.Wellcome Trust Senior Research Fellowship (219447/Z/19/Z), Wellcome Trust Senior Research Fellowship (106207/Z/14/Z), Biotechnology and Biological Sciences Research Council Research Grant (BB/M021424/1), Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (098406/Z/12/B)

DNA Aptamers against the Lup an 1 Food Allergen

Using in vitro selection, high affinity DNA aptamers to the food allergen Lup an 1, ß-conglutin, were selected from a pool of DNA, 93 bases in length, containing a randomised sequence of 49 bases. ß-conglutin was purified from lupin flour and chemically crosslinked to carboxylated magnetic beads. Peptide mass fingerprinting was used to confirm the presence of the ß-conglutin. Single stranded DNA was generated from the randomised pool using T7 Gene 6 Exonuclease and was subsequently incubated with the magnetic beads and the captured DNA was released and amplified prior to a further round of Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Evolution was monitored using enzyme linked oligonucleotide assay and surface plasmon resonance. Once a plateau in evolution was reached, the isolated DNA sequences were cloned and sequenced. The consensus motif was identified via alignment of the sequences and the affinities of these sequences for immobilised ß-conglutin were determined using surface plasmon resonance. The selected aptamer was demonstrated to be highly specific, showing no cross-reactivity with other flour ingredients or with other conglutin fractions of lupin. The secondary structures of the selected aptamers were predicted using m-fold. Finally, the functionality of the selected aptamers was demonstrated using a competitive assay for the quantitative detection of ß-conglutin. . Future work will focus on structure elucidation and truncation of the selected sequences to generate a smaller aptamer for application to the analysis of the Lup an 1 allergen in foodstuffs

Salivary Gland Transcriptomes and Proteomes of Phlebotomus tobbi and Phlebotomus sergenti, Vectors of Leishmaniasis

Phlebotomine female sand flies require a blood meal for egg development, and it is during the blood feeding that pathogens can be transmitted to a host. Leishmania parasites are among these pathogens and can cause disfiguring cutaneous or even possibly fatal visceral disease. The Leishmania parasites are deposited into the bite wound along with the sand fly saliva. The components of the saliva have many pharmacologic and immune functions important in blood feeding and disease establishment. In this article, the authors identify and investigate the protein components of saliva of two important vectors of leishmaniasis, Phlebotomus tobbi and P. sergenti, by sequencing the transcriptomes of the salivary glands. We then compared the predicted protein sequences of these salivary proteins to those of other bloodsucking insects to elucidate the similarity in composition, structure, and enzymatic activity. Finally, this descriptive analysis of P. tobbi and P. sergenti transcriptomes can aid future research in identifying molecules for epidemiologic assays and in investigating sand fly-host interactions

Hyaluronidase of Bloodsucking Insects and Its Enhancing Effect on Leishmania Infection in Mice

Hyaluronidases are enzymes degrading the extracellular matrix of vertebrates. Bloodsucking insects use them to cleave the skin of the host, enlarge the feeding lesion and acquire the blood meal. In addition, resulting fragments of extracellular matrix modulate local immune response of the host, which may positively affect transmission of vector-borne diseases, including leishmaniasis. Leishmaniases are diseases with a wide spectrum of clinical forms, from a relatively mild cutaneous affection to life-threatening visceral disease. Their causative agents, protozoans of the genus Leishmania, are transmitted by phlebotomine sand flies. Sand fly saliva was described to enhance Leishmania infection, but the information about molecules responsible for this exacerbating effect is still very limited. In the present work we demonstrated hyaluronidase activity in salivary glands of various Diptera and in fleas. In addition, we showed that hyaluronidase exacerbates Leishmania lesions in mice and propose that salivary hyaluronidase may facilitate the spread of other vector-borne microorganisms

The predictive value of early behavioural assessments in pet dogs: a longitudinal study from neonates to adults

Studies on behavioural development in domestic dogs are of relevance for matching puppies with the right families, identifying predispositions for behavioural problems at an early stage, and predicting suitability for service dog work, police or military service. The literature is, however, inconsistent regarding the predictive value of tests performed during the socialisation period. Additionally, some practitioners use tests with neonates to complement later assessments for selecting puppies as working dogs, but these have not been validated. We here present longitudinal data on a cohort of Border collies, followed up from neonate age until adulthood. A neonate test was conducted with 99 Border collie puppies aged 2–10 days to assess activity, vocalisations when isolated and sucking force. At the age of 40–50 days, 134 puppies (including 93 tested as neonates) were tested in a puppy test at their breeders' homes. All dogs were adopted as pet dogs and 50 of them participated in a behavioural test at the age of 1.5 to 2 years with their owners. Linear mixed models found little correspondence between individuals' behaviour in the neonate, puppy and adult test. Exploratory activity was the only behaviour that was significantly correlated between the puppy and the adult test. We conclude that the predictive validity of early tests for predicting specific behavioural traits in adult pet dogs is limited