Temporin G, an amphibian antimicrobial peptide against influenza and parainfluenza respiratory viruses: Insights into biological activity and mechanism of action.

Treatment of respiratory viral infections remains a global health concern, mainly due to the inefficacy of available drugs. Therefore, the discovery of novel antiviral compounds is needed; in this context, antimicrobial peptides (AMPs) like temporins hold great promise. Here, we discovered that the harmless temporin G (TG) significantly inhibited the early life-cycle phases of influenza virus. The in vitro hemagglutinating test revealed the existence of TG interaction with the viral hemagglutinin (HA) protein. Furthermore, the hemolysis inhibition assay and the molecular docking studies confirmed a TG/HA complex formation at the level of the conserved hydrophobic stem groove of HA. Remarkably, these findings highlight the ability of TG to block the conformational rearrangements of HA2 subunit, which are essential for the viral envelope fusion with intracellular endocytic vesicles, thereby neutralizing the virus entry into the host cell. In comparison, in the case of parainfluenza virus, which penetrates host cells upon a membrane-fusion process, addition of TG to infected cells provoked ~1.2 log reduction of viral titer released in the supernatant. Nevertheless, at the same condition, an immunofluorescent assay showed that the expression of viral hemagglutinin/neuraminidase protein was not significantly reduced. This suggested a peptide-mediated block of some late steps of viral replication and therefore the impairment of the extracellular release of viral particles. Overall, our results are the first demonstration of the ability of an AMP to interfere with the replication of respiratory viruses with a different mechanism of cell entry and will open a new avenue for the development of novel therapeutic approaches against a large variety of respiratory viruses, including the recent SARS-CoV2.

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema.

BACKGROUND AND OBJECTIVE: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of "vascular preconditioning" predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls. METHODS: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. RESULTS: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 µm), increased apical, internal, and external diameter (28 vs 22 µm; 22 vs 20 µm; and 81 vs 65 µm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. CONCLUSIONS: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema.

Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema: From Bed to Bench.

BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.

Hay or silage? How the forage preservation method changes the volatile compounds and sensory properties of Caciocavallo cheese.

The aim of this study was to determine the effect of the forage preservation method (silage vs. hay) on volatile compounds and sensory properties of a traditional Caciocavallo cheese during ripening. A brown-midrib sudangrass hybrid was cultivated on a 7-ha field and at harvesting it was half ensiled in plastic silo bags and half dried to hay. Forty-four lactating cows were equally allotted into 2 groups fed a isonitrogenous and isoenergetic total mixed ration containing as the sole forage either sorghum hay (H group) or sorghum silage (S group). Milk from the 2 groups was used to produce 3 batches/diet of Caciocavallo ripened for 30, 60, and 90 d. Milk yield and composition as well as cheese chemical and fatty acid composition were not markedly affected by the diet treatment and ripening time. By contrast, ripening induced increased levels of the appearance attribute "yellowness," along with the "overall flavor," the odor/flavor attributes "butter" and "hay," the "salty," "bitter," and "umami" tastes, and the texture attribute "oiliness," whereas the appearance attribute "uniformity" and the texture attribute "elasticity" were reduced. The silage-based diet induced higher perceived intensities of several attributes such as "yellowness"; "overall flavor"; "butter"; "grass" and "hay" odor/flavors; "salty," "bitter," and "umami" tastes; and "tenderness" and "oiliness" textures. In S cheese we also observed higher amounts of ketones and fatty acids. Conversely, H cheese showed the terpene α-pinene, which was not detected in S cheese, and a higher intensity of the appearance attribute "uniformity." These differences allowed the trained panel to discriminate the products, determined an increased consumer liking for 90-d ripened cheese, and tended to increase consumer liking for hay cheese.

Experimental Evidence for Static Charge Density Waves in Iron Oxypnictides.

In this Letter we report high-resolution synchrotron x-ray powder diffraction and transmission electron microscope analysis of Mn-substituted LaFeAsO samples, demonstrating that a static incommensurate modulated structure develops across the low-temperature orthorhombic phase, whose modulation wave vector depends on the Mn content. The incommensurate structural distortion is likely originating from a charge-density-wave instability, a periodic modulation of the density of conduction electrons associated with a modulation of the atomic positions. Our results add a new component in the physics of Fe-based superconductors, indicating that the density wave ordering is charge driven.

Like a pig out of water: seaborne spread of domestic pigs in Southern Italy and Sardinia during the Bronze and Iron Ages.

Southern Italy has a long history of human occupation and passage of different cultures since the Early Holocene. Repeated, ancient introductions of pigs in several geographic areas in Europe make it difficult to understand pig translocation and domestication in Italy. The archeozoological record may provide fundamental information on this, hence shedding light on peopling and on trading among different ancient cultures in the Mediterranean. Yet, because of the scanty nature of the fossil record, ancient remains from human-associated animals are somewhat rare. Fortunately, ancient DNA analysis as applied to domestic species proved to be a powerful tool in revealing human migrations. Herein, we analyzed 80-bp fragment of mitochondrial DNA control region from 27 Sus scrofa ancient samples retrieved from Southern Italian and Sardinian archeological sites, spanning in age from the Mesolithic to the Roman period. Our results surprisingly indicate the presence of the Near Eastern haplotype Y1 on both Italy's major islands (Sardinia and Sicily) during the Bronze Age, suggesting the seaborne transportation of domestic pigs by humans at least during 1600-1300 BC. The presence of the Italian E2 clade in domestic contexts shows that the indigenous wild boar was effectively domesticated or incorporated into domestic stocks in Southern Italy during the Bronze Age, although the E2 haplotype has never been found in modern domestic breeds. Pigs belonging to the endemic E2 clade were thus traded between the Peninsula and Sardinia by the end of the second millennium BC and this genetic signature is still detected in Sardinian feral pigs.

Vertical heterostructure of graphite-MoS2 for gas sensing.

2D materials, given their form-factor, high surface-to-volume ratio, and chemical functionality have immense use in sensor design. Engineering 2D heterostructures can result in robust combinations of desirable properties but sensor design methodologies require careful considerations about material properties and orientation to maximize sensor response. This study introduces a sensor approach that combines the excellent electrical transport and transduction properties of graphite film with chemical reactivity derived from the edge sites of semiconducting molybdenum disulfide (MoS2) through a two-step chemical vapour deposition method. The resulting vertical heterostructure shows potential for high-performance hybrid chemiresistors for gas sensing. This architecture offers active sensing edge sites across the MoS2 flakes. We detail the growth of vertically oriented MoS2 over a nanoscale graphite film (NGF) cross-section, enhancing the adsorption of analytes such as NO2, NH3, and water vapor. Raman spectroscopy, density functional theory calculations and scanning probe methods elucidate the influence of chemical doping by distinguishing the role of MoS2 edge sites relative to the basal plane. High-resolution imaging techniques confirm the controlled growth of highly crystalline hybrid structures. The MoS2/NGF hybrid structure exhibits exceptional chemiresistive responses at both room and elevated temperatures compared to bare graphitic layers. Quantitative analysis reveals that the sensitivity of this hybrid sensor surpasses other 2D material hybrids, particularly in parts per billion concentrations.

Expression and function of Angiopoietins and their tie receptors in human basophils and mast cells.

The Angiopoietin/Tie system is a key regulator of vascular remodeling, maturation, angiogenesis and lymphangiogenesis. In humans there are three angiopoietins: Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2), and Angiopoietin-4 (Ang4). Ang1 and Ang2 are the best characterized angiopoietins. The angiopoietin receptor system consists of two type I tyrosine kinase receptors (Tie1 and Tie2). Tie2 binds all known angiopoietins. We sought to characterize Ang1, Ang2, Tie1 and Tie2 expression and functions in human basophils and mast cells. Basophils, LAD-2 cells and Human Lung Mast Cells (HLMCs) constitutively express Ang1 and Ang2 mRNA. Intracellular staining for Ang1 and Ang2 was stronger in basophils than in mast cells. Immunoelectron microscopy demonstrated Ang1 in cytoplasmic vesicles of basophils. The protein kinase C activators phorbol diester (PMA) and bryostatin 1 (Bryo1) stimulated basophils to rapidly release a large amount of Ang1. PMA-induced Ang1 release was inhibited by brefeldin A. Tie1 and Tie2 mRNAs were expressed in basophils, LAD-2 and HLMCs. Basophils, LAD-2 and HLMCs expressed Tie1 on the cell surface. HLMCs and LAD-2 expressed Tie2 on the cell surface, whereas basophils did not. Ang1, but not Ang2, induced migration of mast cells through the engagement of Tie2. Neither Ang1 nor Ang2 induced basophil chemotaxis. We have identified a novel mechanism of cross-talk between human basophils and mast cells mediated by the Ang1/Tie2 system that might be relevant in the orchestration of inflammatory and neoplastic angiogenesis.

Laser synthesis of ligand-free bimetallic nanoparticles for plasmonic applications.

A picosecond laser ablation approach has been developed for the synthesis of ligand-free AuAg bimetallic NPs where the relative amount of Ag is controlled in situ through a laser shielding effect. Various measurements, such as optical spectroscopy, transmission electron microscopy combined with energy dispersive X-ray spectroscopy and inductively coupled plasma optical emission spectrometry, revealed the generation of homogenous 15 nm average size bimetallic NPs with different compositions and tunable localized surface plasmon resonance. Furthermore, ligand-free metallic nanoparticles with respect to chemically synthesized nanoparticles display outstanding properties, i.e. featureless Raman background spectrum, which is a basic requirement in many plasmonic applications such as Surface Enhanced Raman Spectroscopy. Various molecules were chemisorbed on the nanoparticle and SERS investigations were carried out, by varying the laser wavelength. The SERS enhancement factor for AuAg bimetallic NPs shows an enhancement factor of about 5.7 × 10(5) with respect to the flat AuAg surface.

Compositional and Morphological Characterization of 'Sorrento' and 'Chandler' Walnuts.

In Italy, most of the cultivated walnuts belong to the Sorrento ecotype, and they are considered commercially valuable due to their specific organoleptic characteristics. The aim of this study is to evaluate and compare the morphological and compositional characteristics of walnuts sampled from 'Sorrento' trees cultivated in different locations in Campania and trees of both the 'Chandler' and 'Sorrento' varieties derived from the same location. The results demonstrated that 'Sorrento' and 'Chandler' walnuts have different biometric characteristics and a different fat content, with the highest fat content being found in the 'Sorrento' variety. Regarding the fatty acid (FA) composition, the content of monounsaturated and saturated fatty acids (MUFAs and SFAs) was highest in the 'Sorrento' variety (from 13 to 15% for MUFAs and from 11 to 13% for SFAs), while the polyunsaturated fatty acids (PUFAs) content was highest in the 'Chandler' variety (77%). The total phenolics content (TPC) was highest in the 'Sorrento' variety (from 910 to 1230 mg GAE/100 g), while no difference in γ-tocopherol content was found. Furthermore, the influence of walnut area cultivation was shown for fat content, FA composition and TPC. Therefore, both walnut varieties demonstrated good nutritional properties considering the PUFAs and γ-tocopherol content.

Angiogenesis and lymphangiogenesis in bronchial asthma.

Neovascularization plays a prominent role in inflammation and tissue remodeling in several chronic inflammatory disorders. Vessel number and size, vascular surface area and vascular leakage are all increased in biopsies from patients with asthma. High levels of VEGF and other angiogenic factors have been detected in tissues and biological samples of patients with asthma and correlate with disease activity and inversely with airway hyper-responsiveness. Inflammation in the lung stimulates the growth of new blood vessels and these contribute to the airway obstruction or airway hyper-responsiveness, or both. Effector cells of inflammation (human lung mast cells, basophils, eosinophils, macrophages, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. Inhaled corticosteroids reduce vascularity and growth factor expression and might modulate bronchial vascular remodeling in asthma. Specific antagonists to VEGF and other angiogenic factors and their receptors might help to control chronic airway inflammation and vascular remodeling and offer a novel approach for the treatment of chronic inflammatory lung disorders.

Immunocompromised patients with HBsAg a determinant mutants: comparison of HBsAg diagnostic assays.

Hepatitis B surface antigen (HBsAg) is considered the best marker for the diagnosis of hepatitis B virus (HBV) infection. Mutations of the s gene involving amino acid substitutions within the a determinant could affect the sensitivity of diagnostic tests. In the present study, HBsAg mutants were detected in 3 immunocompromised patients, previously found to be HBsAg negative and anti-HBs positive. All patients had high levels of HBV-DNA, whereas HBsAg tests gave discordant results. Immunosuppression can cause viral reactivation of occult HBV infection in these patients and favour the selection of HBsAg a determinant mutants.

High- and low-frequency noise in Cs and in liquid metal ion sources.

Fundamental Physics space missions set rigid thrust noise limits for liquid metal ion thrusters used as actuators on drag-free platforms aboard the spacecraft. We have measured current-, voltage- and thrust noise of Cs and In LMIS, foreseen as prime candidates in these missions. In the high-frequency range, quasiperiodic oscillations around approximately 10(5)Hz can be observed for both types of emitters with frequency depending on emission current. In the low-frequency range (1-10(-3)Hz), which is particularly important for drag-free control, different types of noise events are observed, which in some instances show definite signs of deterministic chaos (period doubling, self-similarity). High-frequency current oscillations are generally ascribed to electro-hydrodynamic oscillations of the TAYLOR cone and the jet at its apex, with concomitant emission of charged nanodroplets. Comparison of theory and experiment shows unsatisfactory agreement in predicted vs. measured current oscillation frequencies and large disagreement in droplet emission frequencies. No theory is presently available for describing low-frequency noise events. In terms of a linearized Mair theory it is, however, shown that these noise events can be efficiently described by spontaneous variations in electrical emitter impedance. In spite of this impedance noise, the mission requirements for thrust noise (<0.1microN/Hz(1/2)) can be met by a thrust-stabilized In emitter.

Liquid-metal-ion source development for space propulsion at ARC.

The Austrian Research Centers have a long history of developing indium Liquid-Metal-Ion Source (LMIS) for space applications including spacecraft charging compensators, SIMS and propulsion. Specifically the application as a thruster requires long-term operation as well as high-current operation which is very challenging. Recently, we demonstrated the operation of a cluster of single LMIS at an average current of 100muA each for more than 4800h and developed models for tip erosion and droplet deposition suggesting that such a LMIS can operate up to 20,000h or more. In order to drastically increase the current, a porous multi-tip source that allows operation up to several mA was developed. Our paper will highlight the problem areas and challenges from our LMIS development focusing on space propulsion applications.

Antiphospholipid antibodies and acute-phase response in non-metastatic colorectal cancer patients.

AIM: To investigate the plasma levels and prevalence of the most common antiphospholipid antibodies, as well as their relationships with several plasma markers of inflammation, in order to characterize some aspects of cancer thrombophilia. MATERIALS AND METHODS: Eighty-three cancer patients with non-metastatic colorectal solid tumors and 94 control subjects were tested for the presence of IgG/IgM/IgA anti-cardiolipin and anti-Beta2-glycoprotein I antibodies and of several acute-phase reactants, i.e., fibrinogen, factor VIII:C and C4b-binding protein. RESULTS: In cancer patients the plasma levels of the acute-phase reactants and the IgA/IgG anti-cardiolipin and IgA anti-Beta2- glycoprotein I antibodies were significantly higher; the acute-phase reactants were significantly correlated with anti-cardiolipin antibodies; the prevalence of antiphospholipid antibodies was not significantly higher. CONCLUSIONS: In patients with non-metastatic colorectal cancer the acute-phase response is associated with antiphospholipid generation. This could represent a further pathogenetic mechanism for the short-term post-surgery thrombotic complications of patients with colorectal cancer.

[Postoperative acute pancreatitis: our experience and review of the literature]. / Pancreatite acuta postoperatoria: esperienza personale e revisione della letteratura.

AIM: Acute postoperative pancreatitis is a rare event, but, at the same time, it represents one of the most frightening complications, because it is associated with high mortality risk. METHODS: From January 1985 to December 2005, we observed 30 cases (12 males, 18 females) of acute postoperative pancreatitis. Twenty cases of low and medium gravity have been treated with only medical therapy, 10 cases, instead, have requested surgical therapy (necrosectomy and application of abdominal drains in 7 cases, necrosectomy and ileostomy in 1 case, necrosectomy and colostomy in 1 case, ligation of pancreatic vessels in 1 case of haemorrhagic pancreatitis). RESULTS: In the form of low and medium gravity, fast and pharmacological support (somatostatin and gabexate mesilate) are enough to resolve the event. In the form of high gravity the early surgical treatment has represented the clinical solution in 7 patients, while 3 others patients have died for septic and metabolic complication. CONCLUSIONS: Still today acute postoperative pancreatitis represents a frightening complication associated with high mortality risk that the surgeon has to treat with great care to avoid each bilio-pancreatic injury.

Immunopathogenesis of psoriasis and psoriatic arthritis and pharmacological perspectives.

Psoriasis and psoriatic arthritis are chronic inflammatory disorders resulting from a combination of genetic and environmental factors, though the precise causal agents have not yet been identified. The immune system has a major role in their development and the possibility exists that self antigens or antigens from microbial agents, or microbial superantigens initiate a vigorous immune response. Different subsets of T-lymphocytes and dendritic cells, mast cells and granulocytes participate in the pathogenesis and several cytokines and chemokines have been identified in tissue lesions. TNF-alpha is a key proinflammatory cytokine with important pathogenetic role in psoriasis and psoriatic arthritis. Evidence from clinical trials targeting the TNF-alpha-TNF-alpha-receptor supports a central role for this cytokine in the pathogenesis of psoriasis and psoriatic arthritis. Angiogenesis is a prominent early event in lesional psoriatic skin and in synovial membrane psoriatic arthritis. Future potential targets in the treatment of these disorders include biologic agents aimed at blockade of other cytokines, chemokines and angiogenic factors.

Imaging and structural studies of DNA-protein complexes and membrane ion channels.

In bio-imaging by electron microscopy, damage of the sample and limited contrast are the two main hurdles for reaching high image quality. We extend a new preparation method based on nanofabrication and super-hydrophobicity to the imaging and structural studies of nucleic acids, nucleic acid-protein complexes (DNA/Rad51 repair protein complex) and neuronal ion channels (gap-junction, K+ and GABAA channels) as paradigms of biological significance and increasing complexity. The preparation method is based on the liquid phase and is compatible with physiological conditions. Only in the very last stage, samples are dried for TEM analysis. Conventional TEM and high-resolution TEM (HRTEM) were used to achieve a resolution of 3.3 and 1.5 Å, respectively. The EM dataset quality allows the determination of relevant structural and metrological information on the DNA structure, DNA-protein interactions and ion channels, allowing the identification of specific macromolecules and their structure.

[Spontaneous rupture of common iliac artery: a case of Ehlers-Danlos syndrome and review of the literature]. / Rottura spontanea di arteria iliaca comune: descrizione di un caso di sindrome di Ehlers-Danlos e revisione della letteratura.

Authors report an uncommon case of spontaneous rupture of common iliac artery in a man 43 years old with Ehlers-Danlos syndrome. The clinical presentation was devious in the beginning and catastrophic after few hours with a haemo-peritoneum and haemorragic shock. The Ehlers-Danlos syndrome is a rare affection of the connective tissue with an incidence of 1/5000, representing one of the most common disorders of the connective tissue. This disease is characterized by the fragility of arteries, intestine and uterus. Its presentation is often catastrophic, with rupture of a big artery, rupture of uterus during pregnancy or bowel perforation. The mean age of death in subjects with Ehlers-Danlos syndrome is 45 years. This syndrome is inherited in most cases in an autosomal dominant manner; 50% of the cases are due to new mutations. A minority of cases, due to deficit of tenascina X, is inherited in an autosomal recessive manner.

[Appendiceal mucocele due to mucinous cystadenoma: case report and review of the literature]. / Mucocele appendicolare da cistoadenoma mucinoso: descrizione di un caso clinico e revisione della letteratura.

Mucinous cystadenomas of the appendix are rare tumours. In this article we describe the case of a young woman who presented with abdominal pain and a clinical pattern likely to a chronic appendicitis. At laparotomy we found a dilatation of the appendix which contained an abundant quantity of mucus. Histological examination showed a mucinous cystadenoma of the appendix. This neoplasm requires a surgical treatment, usually only appendectomy and right hemicolectomy in case of involvement of the caecum. During operation, the surgeon must take care in handling the appendix because of the risk of rupture with consequent dissemination of epithelial cells in the peritoneal cavity (pseudomyxoma peritonei).