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Occupational ergonomics aims to optimize the work environment and to enhance both productivity and worker well-being. Work-related exposure assessment, such as lifting loads, is a crucial aspect of this discipline, as it involves the evaluation of physical stressors and their impact on workers' health and safety, in order to prevent the development of musculoskeletal pathologies. In this study, we explore the feasibility of machine learning (ML) algorithms, fed with time- and frequency-domain features extracted from inertial signals (linear acceleration and angular velocity), to automatically and accurately discriminate safe and unsafe postures during weight lifting tasks. The signals were acquired by means of one inertial measurement unit (IMU) placed on the sternums of 15 subjects, and subsequently segmented to extract several time- and frequency-domain features. A supervised dataset, including the extracted features, was used to feed several ML models and to assess their prediction power. Interesting results in terms of evaluation metrics for a binary safe/unsafe posture classification were obtained with the logistic regression algorithm, which outperformed the others, with accuracy and area under the receiver operating characteristic curve values of up to 96% and 99%, respectively. This result indicates the feasibility of the proposed methodology—based on a single inertial sensor and artificial intelligence—to discriminate safe/unsafe postures associated with load lifting activities. Future investigation in a wider study population and using additional lifting scenarios could confirm the potentiality of the proposed methodology, supporting its applicability in the occupational ergonomics field. [ABSTRACT FROM AUTHOR]

Using a rat model of type 1 diabetes (T1D) obtained by treatment with streptozotocin, an antibiotic that destroys pancreatic β‐cells, we evaluated the influence of subsequent hyperglycemia on the morphology and physiology of the Harderian gland (HG). HG is located in the medial corner of the orbit of many terrestrial vertebrates and, in rodents, is characterized by the presence of porphyrins, which being involved in the phototransduction, through photo‐oxidation, produce reactive oxygen species activating the autophagy pathway. The study focused on the expression of some morphological markers involved in cell junction formation (occludin, connexin‐43, and α‐tubulin) and mast cell number (MCN), as well as autophagic and apoptotic pathways. The expression of enzymes involved in steroidogenesis [steroidogenic acute regulatory protein (StAR), and 3β‐hydroxysteroid dehydrogenase (3β‐HSD)] and the level of lipid peroxidation by thiobarbituric acid reactive species assay were also evaluated. The results strongly indicate, for the first time, that T1D has a negative impact on the pathophysiology of rat HG, as evidenced by increased oxidative stress, morphological and biochemical alterations, hyperproduction and secretion of porphyrins, increased MCN, reduced protein levels of StAR and 3β‐HSD, and, finally, induced autophagy and apoptosis. All the combined data support the use of the rat HG as a suitable experimental model to elucidate the molecular damage/survival pathways elicited by stress conditions. [ABSTRACT FROM AUTHOR]

Quercetin is a hydrophobic molecule with short blood circulation times and instability. The development of a nano-delivery system formulation of quercetin may increase its bioavailability, resulting in greater tumor suppressing effects. Triblock ABA type polycaprolactone-polyethylenglycol- polycaprolactone (PCL-PEG-PCL) copolymers have been synthetized using ring-opening polymerization of caprolactone from PEG diol. The copolymers were characterized by nuclear magnetic resonance (NMR), diffusion-ordered NMR spectroscopy (DOSY), and gel permeation chromatography (GPC). The triblock copolymers self-assembled in water forming micelles consisting of a core of biodegradable polycaprolactone (PCL) and a corona of polyethylenglycol (PEG). The core-shell PCL-PEG-PCL nanoparticles were able to incorporate quercetin into the core. They were characterized by dynamic light scattering (DLS) and NMR. The cellular uptake efficiency of human colorectal carcinoma cells was quantitatively determined by flow cytometry using nanoparticles loaded with Nile Red as hydrophobic model drug. The cytotoxic effect of quercetin-loaded nanoparticles was evaluated on HCT 116 cells, showing promising results. [ABSTRACT FROM AUTHOR]

Recent years have seen a significant increase in the scientific literature related to various methods for analyzing oxidative potential (OP) of atmospheric particulate matter (PM). The presence of several types of PM, differing chemical and physical properties, released by both anthropogenic and natural sources, leads to numerous health issues in living organisms and represents an attractive target for air quality monitoring. Therefore, several studies have focused on developing rapid and self-operative tests, employing different target molecules to assess OP of atmospheric aerosols as well as unique approaches to overcome some of the most common laboratory-related issues in this kind of analysis. This work provides an overview of online and automated systems, as well as a broad picture of the state-of-art of the various devices and methods developed on this topic over the last two decades. Moreover, representative studies on this subject will be discussed, analyzing the advantages and drawbacks of the developed automated techniques. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is still the leading global cause of death from an infectious bacterial agent. Limiting tuberculosis epidemic spread is therefore an urgent global public health priority. As stated by the WHO, to stop the spread of the disease we need a new vaccine, with better coverage than the current Mycobacterium bovis BCG vaccine. This vaccine was first used in 1921 and, since then, there are still no new licensed tuberculosis vaccines. However, there is extremely active research in the field, with a steep acceleration in the past decades, due to the advance of technologies and more rational vaccine design strategies. This review aims to gather latest updates in vaccine development in the various clinical phases and to underline the contribution of Structural Vaccinology (SV) to the development of safer and effective antigens. In particular, SV and the development of vaccine adjuvants is making the use of subunit vaccines, which are the safest albeit the less antigenic ones, an achievable goal. Indeed, subunit vaccines overcome safety concerns but need to be rationally re-engineered to enhance their immunostimulating effects. The larger availability of antigen structural information as well as a better understanding of the complex host immune response to TB infection is a strong premise for a further acceleration of TB vaccine development. [ABSTRACT FROM AUTHOR]

Purpose: Here, we report, for the first time, the temporal expression and localization of axonemal radial spoke head homolog A (RSPH6A) protein during the first wave of rat spermatogenesis and in oxidative stress conditions. Methods: For the developmental study, testes were collected from rats at different developmental stages (7, 14, 21, 28, 35, 42, and 60 postnatal days); for in vivotreatment, 24 rats were treated with cadmium and/or melatonin. From each sample, western blot (WB) and immunofluorescence (IF) analyses for RSPH6A were performed. Results: RSPH6A expression starts at 21 PND alongside the appearance of I spermatocytes (SPC) with a significant increase up to 60 PND. Data were confirmed by IF analysis, showing that RPSH6A expression is restricted to I and II SPC, spermatids, and mature sperm. In vivo experiments showed that the expression and localization of RSPH6A in the testis and epididymal spermatozoa of adult rats treated with cadmium were impaired. Interestingly, melatonin (an antioxidant), given together with Cd, can counteract its damaging effects. Conclusions: All combined data confirm that RSPH6A contributes to the onset of fertility by acting on sperm motility, raising the possibility of using RSPH6A as a marker for normal fertility in the general population. [ABSTRACT FROM AUTHOR]

Herein is reported, for the first time in the rat Harderian gland (HG), the counteractive action of melatonin (Mlt), a well‐known antioxidant radical scavenger, on the increased oxidative stress damages induced by a pro‐oxidant substance, cadmium (Cd), an environmental pollutant also considered as endocrine disruptor. HG, an infraorbital gland present in almost all terrestrial vertebrates, produces a lipid secretion to lubricate the eyeball, as well as porphyrin/Mlt as light transducers. Moreover, HG is an extra‐gonadal source of steroid sex hormones. Via ex vivo experiments lasting for 24 h, we verified the increased lipid peroxidation in Cd‐treated glands, producing morphological alteration of the glandular epithelium, as well as an increased porphyrins accumulation. Moreover, Cd also induced a decreased protein level of the steroidogenic enzymes steroidogenic acute regulatory (StAR) and 3βHSD, and an increased mast cell number. Results obtained with Mlt cotreatment demonstrated that it decreased the levels of Cd‐induced oxidative damage, with reversal of all the observed modification. Furthermore, the TUNEL assay showed that the increased number of apoptotic cells in Cd‐treated HG was counteracted by the contemporaneous Mlt administration. Results confirmed that Mlt treatment restored the levels of two autophagy markers, LC3 and p62, counteracting the autophagy Cd‐induced. Interestingly, the positive effects of Mlt alone were highlighted by the decreased rate of lipid peroxidation as compared with the control, confirming its antioxidant action. Combined data further confirmed the antioxidant action of Mlt in counteracting the degeneration provoked by reactive oxygen species (ROS) in the rat HG, a tissue extremely susceptible to oxidative stress condition. Research Highlights: –Oxidative stress Cd‐induced produces morphological and biochemical alteration in the rat Harderian gland.–Melatonin cotreatment counteracts all the damages provoked by oxidative disorders.–Melatonin alone reduces the rate of lipid peroxidation, thanks to its antioxidant properties. [ABSTRACT FROM AUTHOR]

Coronaviruses, including SARS-CoV-2 (the etiological agent of the current COVID-19 pandemic), rely on the surface spike glycoprotein to access the host cells, mainly through the interaction of their receptor-binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2). Therefore, molecular entities able to interfere with the binding of the SARS-CoV-2 spike protein to ACE2 have great potential to inhibit viral entry. Starting from the available structural data on the interaction between SARS-CoV-2 spike protein and the host ACE2 receptor, we engineered a set of soluble and stable spike interactors, here denoted as S-plugs. Starting from the prototype S-plug, we adopted a computational approach by combining stability prediction, associated to single-point mutations, with molecular dynamics to enhance both S-plug thermostability and binding affinity to the spike protein. The best developed molecule, S-plug3, possesses a highly stable α-helical con-formation (with melting temperature Tm of 54 °C) and can interact with the spike RBD and S1 domains with similar low nanomolar affinities. Importantly, S-plug3 exposes the spike RBD to almost the same interface as the human ACE2 receptor, aimed at the recognition of all ACE2-accessing coronaviruses. Consistently, S-plug3 preserves a low nanomolar dissociation constant with the delta B.1.617.2 variant of SARS-CoV-2 spike protein (KD = 29.2 ± 0.6 nM). Taken together, we provide valid starting data for the development of therapeutical and diagnostic tools against coronaviruses accessing through ACE2. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether accelerated brain aging occurs in individuals with mood or psychotic disorders. Methods: A systematic review following PRISMA guidelines was conducted. A meta‐analysis was then performed to assess neuroimaging‐derived brain age gap in three independent groups: (1) schizophrenia and first‐episode psychosis, (2) major depressive disorder, and (3) bipolar disorder. Results: A total of 18 papers were included. The random‐effects model meta‐analysis showed a significantly increased neuroimaging‐derived brain age gap relative to age‐matched controls for the three major psychiatric disorders, with schizophrenia (3.08; 95%CI [2.32; 3.85]; p < 0.01) presenting the largest effect, followed by bipolar disorder (1.93; [0.53; 3.34]; p < 0.01) and major depressive disorder (1.12; [0.41; 1.83]; p < 0.01). The brain age gap was larger in older compared to younger individuals. Conclusion: Individuals with mood and psychotic disorders may undergo a process of accelerated brain aging reflected in patterns captured by neuroimaging data. The brain age gap tends to be more pronounced in older individuals, indicating a possible cumulative biological effect of illness burden. [ABSTRACT FROM AUTHOR]

Insulin-like peptide 3 (INSL3) is a biomarker for Leydig cells in the testes of vertebrates, and it is principally involved in spermatogenesis through specific binding with the RXFP2 receptor. This study reports the insl3 gene transcript and the Insl3 prepropeptide expression in both non-reproductive and reproductive tissues of Danio rerio. An immunohistochemistry analysis shows that the hormone is present at a low level in the Leydig cells and germ cells at all stages of Danio rerio testis differentiation. Considering that the insl3 gene is transcribed in Leydig cells, our results highlight an autocrine and paracrine function of this hormone in the Danio rerio testis, adding new information on the Insl3 mode of action in reproduction. We also show that Insl3 and Rxfp2 belonging to Danio rerio and other vertebrate species share most of the amino acid residues involved in the ligand–receptor interaction and activation, suggesting a conserved mechanism of action during vertebrate evolution. [ABSTRACT FROM AUTHOR]

In a high-tech greenhouse located at Atlacomulco, Mexico State, incidences from 60 to 90% of plants showing symptoms associated to begomoviruses have been observed. The objectives of this study were to identify the begomoviruses present, to know if they are transmitted by seed, to determine the species of whitefly and if they are carriers of the virus. Leaves of adult symptomatic plants were analyzed with universal primers for begomoviruses. Seeds of fruits from positive plants were seeded to obtain seedlings; seeds and seedlings were analyzed by PCR for begomoviruses. Adults whiteflies were analyzed with specific primers to the mitochondrial gene of the cytochrome C oxidase subunit I and universal primers for begomoviruses. Sequences of PCR products from symptomatic plants had 99% of identity with Tomato severe leaf curl virus (ToSLCV). No begomoviruses were detected in seed and seedlings. Sequences from the whiteflies present in the greenhouse had an identity of 99% with Bemisia tabaci and they were carriers of ToSLCV. This is the first report of ToSLCV infecting tomato grown in greenhouse in Mexico. [ABSTRACT FROM AUTHOR]

Hypotrichosis simplex (HS) is a rare form of hereditary alopecia characterized by childhood onset of diffuse and progressive scalp and body hair loss. Although research has identified a number of causal genes, genetic etiology in about 50% of HS cases remains unknown. The present report describes the identification via whole-exome sequencing of five different mutations in the gene LSS in three unrelated families with unexplained, potentially autosomal-recessive HS. Affected individuals showed sparse to absent lanugo-like scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body hair. LSS encodes lanosterol synthase (LSS), which is a key enzyme in the cholesterol biosynthetic pathway. This pathway plays an important role in hair follicle biology. After localizing LSS protein expression in the hair shaft and bulb of the hair follicle, the impact of the mutations on keratinocytes was analyzed using immunoblotting and immunofluorescence. Interestingly, wild-type LSS was localized in the endoplasmic reticulum (ER), whereas mutant LSS proteins were localized in part outside of the ER. A plausible hypothesis is that this mislocalization has potential deleterious implications for hair follicle cells. Immunoblotting revealed no differences in the overall level of wild-type and mutant protein. Analyses of blood cholesterol levels revealed no decrease in cholesterol or cholesterol intermediates, thus supporting the previously proposed hypothesis of an alternative cholesterol pathway. The identification of LSS as causal gene for autosomal-recessive HS highlights the importance of the cholesterol pathway in hair follicle biology and may facilitate novel therapeutic approaches for hair loss disorders in general. [ABSTRACT FROM AUTHOR]

This document is a position paper that discusses the use of sunscreens. It emphasizes the importance of using sunscreen properly and suggests the need for a meeting among scientific experts to improve their composition, particularly for pediatric use. The paper also acknowledges the benefits of sun exposure for physical and mental well-being, but cautions against excessive exposure and the use of tanning beds. It suggests that physical protection and clothing may be preferable to relying solely on sunscreen. The paper raises concerns about the controversial effectiveness of sunscreens in preventing skin cancer and the potential endocrine-disrupting effects of certain chemical filters. It concludes by calling for further research and collaboration to develop the best strategy for sun protection. The document includes a list of references covering various topics related to sun protection, such as the role of vitamin D in melanoma development, risk factors for melanoma, the effectiveness and absorption of sunscreen ingredients, the potential effects of endocrine-disrupting chemicals, and the safety of nanoparticles in sunscreen. These references can be valuable for library patrons conducting research on sun protection and its impact on health and the environment. [Extracted from the article]

The Burkholderia cepacia complex (Bcc) is a group of Gram-negative opportunistic pathogens causing infections in people with cystic fibrosis (CF). Bcc is highly antibiotic resistant, making conventional antibiotic treatment problematic. The identification of novel targets for anti-virulence therapies should improve therapeutic options for infected CF patients. We previously identified that the peptidoglycan-associated lipoprotein (Pal) was immunogenic in Bcc infected CF patients; however, its role in Bcc pathogenesis is unknown. The virulence of a pal deletion mutant (Δ pal) in Galleria mellonella was 88-fold reduced ( p < .001) compared to wild type. The lipopolysaccharide profiles of wild type and Δ pal were identical, indicating no involvement of Pal in O-antigen transport. However, Δ pal was more susceptible to polymyxin B. Structural elucidation by X-ray crystallography and calorimetry demonstrated that Pal binds peptidoglycan fragments. Δ pal showed a 1.5-fold reduced stimulation of IL-8 in CF epithelial cells relative to wild type ( p < .001), demonstrating that Pal is a significant driver of inflammation. The Δ pal mutant had reduced binding to CFBE41o− cells, but adhesion of Pal-expressing recombinant E. coli to CFBE41o− cells was enhanced compared to wild-type E. coli ( p < .0001), confirming that Pal plays a direct role in host cell attachment. Overall, Bcc Pal mediates host cell attachment and stimulation of cytokine secretion, contributing to Bcc pathogenesis. [ABSTRACT FROM AUTHOR]

While the nutritional approaches linked to cardiovascular system, autoimmune system and gastrointestinal tract's functionality is enough investigated instead the skin organ is gaining scientific interest in the last years. The established belief that using food supplements combined with a correct nutritional diet can improve the beauty of skin as an organ is gaining ground in the minds of many of dermatologists. That's why nutraceuticals is becoming an important tool to control oxidative stress and promote a healthy skin. The key concept that vitamin C, which can only taken through diet, is one of the most important micronutrients, since it is involved in the regulation and control of collagenases could be taken as a starting point, along with the fact that foods or supplements containing polyunsaturated fatty acids (PUFA) such as omega-3 have been prescribed in the last few years in different ways for their clinical effectiveness not just on the signs of aging but also in the prevention of aging. [ABSTRACT FROM AUTHOR]

Glycoconjugate vaccines have been effectively used in humans for about 40 years. The glycoconjugates have substituted plain polysaccharide vaccines that have many limitations, especially in infants. The covalent linking of protein to carbohydrates has allowed to overcome T-cell-dependent type-2 response of sugars. Glycoconjugates can show improved responses (over plain saccharides) also in elderly and immunocompromised (and depending on the endpoint also in immunocompetent adults), but infants represent the main target of these vaccines because of their unique immune system. Differently from the plain polysaccharide vaccines, the glycoconjugates are also able to induce Immunoglobulin G (IgG) response in infants. Recently, vaccines containing conjugates directly expressed in Escherichia coli (bioconjugates) have been tested in the clinic against Shigella dysenteriae type 1, uropathogenic E. coli , and Streptococcus pneumoniae. Here, we report an overall comparison of classical- and bioconjugate vaccines in terms of the structural properties and the immunological response elicited. • Chemical conjugates are obtained by covalent coupling of polysaccharide to carrier protein. • Chemical conjugates are a very consolidated platform. • Bioconjugates are conjugates directly expressed in Escherichia coli. • Bioconjugates tested in clinic against Shigella dysenteriae, E.coli and S.pneumoniae. • Overall comparison of characteristics and immunological response of conjugate vaccines. [ABSTRACT FROM AUTHOR]

Monitoring of foetal heart rate and its variability (FHRV) covers an important role in assessing health of foetus. Many analysis methods have been used to get quantitative measures of FHRV. FHRV has been studied in time and in frequency domain and interesting clinical results have been obtained. Nevertheless, a standardized definition of FHRV and a precise methodology to be used for its evaluation are lacking. We carried out a literature overview about both frequency domain analysis (FDA) and time domain analysis (TDA). Then, by using simulated FHR signals, we defined the methodology for FDA. Further, employing more than 400 real FHR signals, we analysed some of the most common indexes, Short Term Variability for TDA and power content of the spectrum bands and sympathovagal balance for FDA, and evaluated their ranges of values, which in many cases are a novelty. Finally, we verified the relationship between these indexes and two important parameters: week of gestation, indicator of foetal growth, and foetal state, classified as active or at rest. Our results indicate that, according to literature, it is necessary to standardize the procedure for FHRV evaluation and to consider week of gestation and foetal state before FHR analysis. [ABSTRACT FROM AUTHOR]

mGlu1 and mGlu5 metabotropic glutamate receptors are expressed in the vertebrate retina, and are co-localized in some retinal neurons. It is believed that both receptors are coupled to polyphosphoinositide (PI) hydrolysis in the retina and their function may diverge in some cells because of a differential engagement of downstream signaling molecules. Here, we show that it is only the mGlu1 receptor that is coupled to PI hydrolysis in the retina. We used either bovine retinal slices or intact mouse retinas challenged with the mixed mGlu1/5 receptor agonist, DHPG. In both models, DHPG-stimulated PI hydrolysis was abrogated by the selective mGlu1 receptor antagonist, JNJ16259685, but was insensitive to the mGlu5 receptor antagonist, MPEP. In addition, the PI response to DHPG was unchanged in the retina of mGlu5 mice but was abolished in the retina of crv4 mice lacking mGlu1 receptors. Stimulation of the mitogen-activated protein kinase pathway by DHPG in intact mouse retinas were also entirely mediated by mGlu1 receptors. Our data provide the first example of a tissue in which a biochemically detectable PI response is mediated by mGlu1, but not mGlu5, receptors. Hence, bovine retinal slices might be used as a model for the functional screening of mGlu1 receptor ligands. In addition, the mGlu1 receptor caters the potential as a drug target in the experimental treatment of degenerative disorders of the retina. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis is a human pathogen causing bacterial meningitis and sepsis. The capsular polysaccharide surrounding N. meningitidis is a major virulence factor. The capsular polysaccharide consists of polyhexosamine phosphates in N. meningitidis serogroups A and X. The capsule polymerases (CPs) of these serogroups are members of the Stealth protein family comprising D-hexose-1-phosphate transferases from bacterial and protozoan pathogens. CslA, one of two putative CPs of the pathophysiologically less relevant N. meningitidis serogroup L, is one of the smallest known Stealth proteins and caught our attention for structure-function analyses. Because the N. meningitidis serogroup L capsule polymer consists of a trimeric repeating unit ([→3)-β-D-GlcNAc-(1→3)-β-D-GlcNAc-(1→3)-α-D-GlcNAc-(13OPO3→]n), we speculated that the two predicted CPs (CslA and CslB) work together in polymer production. Consequently, both enzymes were cloned, overexpressed, and purified as recombinant proteins. Contrary to our expectation, enzymatic testing identified CslB to be sufficient to catalyze the synthesis of the complex trimeric N. meningitidis serogroup L capsule polymer repeating unit. No polymerase activity was detected for CslA, although the enzyme facilitated the hydrolysis of UDP-GlcNAc. Bioinformatics analyses identified two glycosyltransferase (GT) domains in CslB. The N-terminal domain modeled with 100% confidence onto a number of GT-A folded proteins, whereas the C-terminal domain modeled with 100% confidence onto TagF, a GT-B folded teichoic acid polymerase from Staphylococcus epidermidis. Amino acid positions known to have critical catalytic functions in the template proteins were conserved in CslB, and their point mutation abolished enzyme activity. CslB represents an enzyme of so far unique complexity regarding both the catalyzed reaction and enzyme architecture. [ABSTRACT FROM AUTHOR]

Parental phenotype and environment have cascading effects on offspring performance. Such 'maternal' effects are often mediated by the size and quality of the eggs in terms of maternal endogenous substances or exogenous components., Maternal effects can function to maximize parental fitness via adaptive allocation of components among sibling eggs. In birds, the often documented variation in concentration of egg dietary antioxidants or other egg compounds with laying order may thus reflect adaptive parental favouritism or maternal physiological constraints., Vitamins are found in the yolk at high concentrations and accomplish important physiological functions. Tocopherols ('vitamin E') have major roles in antioxidant protection, but the consequence of variation in their concentration for chick phenotype has never been experimentally investigated under a natural selection regime., In the yellow-legged gull ( Larus michahellis) free-ranging population we studied, vitamin E concentration and egg size decline from the first to the third (last) egg. Chicks from third eggs are smaller and have lower viability compared to those from sibling eggs. Here, we tested the effect of injecting a physiological dose of vitamin E in the egg yolk on chick body size at hatching by comparison with chicks from sham-injected eggs., As predicted, chicks from vitamin E injected third eggs were larger than chicks from control third eggs, whereas vitamin E had no effect on chicks from the other eggs. Thus, vitamin E injection disrupted the brood size hierarchy according to laying order normally found in this species., In species that adopt a brood reduction strategy, differential allocation of vitamin E to the eggs can contribute to establish a hierarchy of reproductive value among progeny members functioning to maximize parental fitness. The present results therefore have general implications for the study of the evolution of maternal effects mediated by transfer of potentially limiting maternal antioxidants to the eggs. [ABSTRACT FROM AUTHOR]

A gold nanostructured electrochemical sensor based on modified GC electrode for thiols' detection is described and characterized. This sensor is a suitable device for the measurement of the oxidative potential (OP) of the atmospheric particulate matter (PM), considered a global indicator of adverse health effects of PM, as an alternative to the classic spectrophotometric methods. The operating principle is the determination of the OP, through the measurement of the consumption of DTT content. The DTT-based chemical reactivity is indeed a quantitative acellular probe for assessment of the capacity of the atmospheric PM to catalyze reactive oxygen species generation which contributes to the induction of oxidative stress in living organisms and in turn to the outcome of adverse health effects. To make the sensors, glassy carbon electrodes, traditional (GC) and screen printed (SPE) electrodes, have been electrochemically modified with well-shaped rounded gold nanoparticles (AuNPs) by using a deposition method that allows obtaining a stable and efficient modified surface in a very simple and reproducible modality. The chemical and morphological characterization of the nano-hybrid material has been performed by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy coupled with electron dispersive spectroscopy analysis (SEM/EDS). The electrochemical properties have been evaluated by cyclic voltammetry (CV) and chrono-amperometry (CA) in phosphate buffer at neutral pH as requested in DTT assay for OP measurements. The electroanalytical performances of the sensor in DTT detection are strongly encouraging showing low LODs (0.750 μM and 1.5 μM), high sensitivity (0.0622 μA cm−2 μM−1 and 0.0281 μA cm−2 μM−1), wide linear and dynamic ranges extending over 2-4 orders of magnitude and high selectivity. FIA preliminary results obtained on measuring the DTT rate consumption in six PM aqueous extracts samples showed a good correlation with measurements obtained in parallel on the same set of samples by using the classic spectrophotometric method based on the Ellman's reactive use. These results confirm the high selectivity of the method and its suitability for application to be applied in PM oxidative potential measurements. [Display omitted] • Development of modified GC electrodes with electrodeposited gold nanoparticles. • XPS and SEM/EDS characterization of the GC/AuNPs modified electrodes. • Electrochemical characterization of the GC/AuNPs sensor to detect dithiotreitol (DTT). • Electroanalytical performances of the sensor make it suitable to detect DTT in PM aqueous extracts. • Electrochemical DTT assay as an alternative to classic spectrophotometric assay in OP determination. [ABSTRACT FROM AUTHOR]

Behavioral lateralization at the population level is widespread across vertebrates, with considerable variation among species. However, evidence for individual-level and sex-dependent lateralization is sparse and inconsistent in fish, reptiles and birds. In addition, covariation of lateralization with position in the laying sequence, which is expected because the concentration of maternal egg hormones varies with laying order, has never been investigated. We analyzed lateralization of yellow-legged gull ( Larus michahellis ) chicks in reverting from supine to prone posture (‘RTP’ response) and in pecking at a dummy parental bill to solicit food provisioning (‘begging’ response). Chicks were lateralized both at the population and at the individual level in the RTP response and at the individual level in begging. Lateralization in the RTP was sex-dependent, as females showed a leftward preference. Lateralization in either motor task was not correlated within individuals. Lateralization did not differ among families, suggesting little additive genetic variation. Lateral preference in begging response varied according to laying order and matched variation in egg androgens concentration. Our study confirms previous findings on population-level lateralization and adds to the scant information on individual-level and heritable variation in lateralization in birds. Moreover, it hints at epigenetic components in lateralization depending on maternal effects. [ABSTRACT FROM AUTHOR]

Introduction: The digital divide affecting elderly patients may compromise the diffusion of telemedicine systems for this age segment. It might be that the difficulties in the passage from trials to the effective distribution of telemedicine systems are also due to the awareness of a personal digital divide in the target population. Materials and Methods: The analysis aims to estimate the number of people over the age of 50 years with potential cardiovascular problems able to access the Web. It made use of data from several sources (the Survey of Health, Ageing and Retirement in Europe and the Istituto Nazionale di Statistica Multiscopo Survey). Furthermore, with regard to Italy, the estimates obtained from official data were compared with those obtained in a survey investigating heart failure patients in Tuscany. Results: In 2011, the percentage of people suffering from cardiovascular diseases and with Web access was 24% in Europe, with significant differences by country (ranging from 53% in Switzerland to below 20% in Italy, Spain, and Portugal). In Italy, however, the proportion of people with Web access increased from 2007 to 2011, and the survey in Tuscany showed that elderly people with limited information and communications technology skills overcame challenges and learned how to connect to the Web because they started to appreciate new technologies. Conclusions: The opportunity to use the Internet to monitor patients with chronic disease can serve as a challenge to reduce the digital divide gap and, furthermore, to increase their social and technological inclusion. [ABSTRACT FROM AUTHOR]

The objective of this work was to study the use of electrical impedance spectroscopy (EIS) measurement to characterize muscle electrical properties in different conditions. In vivo EIS measurements were carried out in the range 1–60 kHz on 32 forearm flexor muscles of healthy volunteers. Each subject underwent to a protocol consisting of three trials: rest condition, isometric contraction, 4 min relaxation. Measured data were fitted with Cole–Cole equivalent electrical circuit using the complex nonlinear least square method. Finally, the relative variations from the steady state of the electrical parameters of the equivalent electrical circuit were estimated. Results obtained are in agreement with the hypothesis that, in the frequency range considered, the current preferentially flows through the extracellular fluid, being the component of intracellular resistance negligible. Among circuital parameters, in fact, the relative variations from steady state of R 0 changed highly significant ( p < 0.001) both during contraction and after 4 min relaxation. [ABSTRACT FROM AUTHOR]

Mothers influence their offspring viability by equipping the eggs with immune factors, but sons and daughters can differ in susceptibility to pathogens and in reproductive value. The genes that control immunity also affect melanin-based feather coloration. We analyzed the association between antibody concentration in barn swallow eggs and maternal coloration and found that the amount of antibodies that mothers transferred to eggs depended on which sex prevailed among their offspring.Maternal allocation shapes offspring phenotype by being tailored to parental phenotype and offspring sex. Because melanogenesis and immunity have partly common genetic control, maternal effects via egg immune factors and parental melanization may covary. Here, we tested whether barn swallows Hirundo rustica allocated antibodies against a novel antigen to their eggs according to embryo sex depending on maternal melanin-based coloration while controlling for paternal tail ornamentation. Egg antibody concentration increased with maternal plumage darkness in broods with relatively more females, whereas it decreased in broods with relatively more males. Thus, darker females allocated more antibodies to their eggs when offspring sex ratio was female biased, whereas paler females allocated more antibodies to the eggs when offspring sex ratio was male biased. These effects were independent of laying order. Our results are compatible with the hypotheses that maternal allocation to sons depends on their reproductive value as predicted by heritable melanin-based coloration and with the hypothesis of differential susceptibility of pheomelanic daughters to parasitism. These effects may depend on pleiotropy of the genes that control melanogenesis and immunity, which may differentially act on investment in self-maintenance and maternal effects. This study is the first study in vertebrates of the association between maternal effects on either sex via egg quality and parental melanization. The links between the genetic control of melanogenesis and of major fitness traits like immunity and the role of maternal effects in reproductive strategies prompt for more studies of the covariation between parental coloration and maternal sex-dependent allocation via egg quality. [ABSTRACT FROM PUBLISHER]

Fruit species are an important strategy to guarantee food security and sovereignty for traditional populations. Therefore, the objective of this work was to estimate the richness and record the fruit species cultivated in family farms in the municipality of Santarém, Pará. The survey of fruit species was carried out in 13 homegardens of the families visited, with records of 520 individuals belonging to 39 species, 29 genera and 16 botanical families. Among the evaluated individuals, the families Arecaceae (6 spp.) and Myrtaceae (5 spp.) stood out. On average, 14 fruit species were found per yard, showing that the cultivation of these species is strongly associated with supplying the demand for food for family consumption. Of the fruit species, the most frequent were Persea americana and Cocos nucifera with 100% representation, followed by Theobroma grandiflorum with 92%. The richness of fruit species found in the homegardens of the families visited reveals the importance of these environments in food and nutrition sovereignty and security. In addition, homegardens stand out for their strategic role in introducing trees into agricultural landscapes. In view of this, it is recommended to carry out future work focusing on the role of homegardens in the generation of quality food, aiming to subsidize the promotion of public policies to encourage the production of food in these environments. [ABSTRACT FROM AUTHOR]

Background: Perfusion CT is a technology which allows functional evaluation of tissue vascularity. Due to this potential, it is finding increasing utility in oncology. Although since its introduction continuous advances have interested CT technique, some issues have to be still defined, concerning both clinical and technical aspects. In this study, we dealt with the comparison of two widely employed mathematical models (dual input one compartment model – DOCM - and maximum slope – SM -) analyzing their robustness to the noise. Methods: We carried out a computer simulation process to quantify effect of noise on the evaluation of an important perfusion parameter (Arterial Blood Flow – BFa) in liver tumours. A total of 4500 liver TAC, corresponding to 3 fixed BFa values, were simulated using different arterial and portal TAC (computed from 5 real CT images) at 10 values of signal to noise ratio (SNR). BFa values were calculated by applying four different algorithms, specifically developed, to these noisy simulated curves. Three algorithms were developed to implement SM (one semiautomatic, one automatic and one automatic with filtering) and the last for the DOCM method. Results: In all the simulations, DOCM provided the best results, i.e., those with the lowest percentage error compared to the reference value of BFa. Concerning SM, the results are variable. Results obtained with the automatic algorithm with filtering are close to the reference value, but only if SNR is higher than 50. Vice versa, results obtained by means of the semiautomatic algorithm gave, in all simulations, the lowest results with the lowest standard deviation of the percentage error. Conclusions: Since the use of DOCM is limited by the necessity that portal vein is visible in CT scans, significant restriction for patients’ follow-up, we concluded that SM can be reliably employed. However, a proper software has to be used and an estimation of SNR would be carried out. [ABSTRACT FROM AUTHOR]

Introduction: Telemedicine systems consist of collection, transmission, and analysis of biometric data essentially based on instrumental measures. Our goal was to evaluate if information collected from patients has an incremental informative value in automatically rating the patient's health status. Materials and Methods: We present preliminary results of a new telemedicine system (ASCOLTA) obtained by observation of 12 heart failure patients (New York Heart Association Class IIb-III). Instrumental data (electrocardiogram, oxygen saturation level, and respiration rate) were wirelessly collected daily together with clinical data (weight, heart rate, and blood pressure values) and patients' information obtained through a Web-based questionnaire, simulating a virtual medical visit. Health status was independently judged by two blinded cardiologists and by the patient's cardiologist on the basis of 348 daily clinical reports. Random forest classification analysis was applied to 240 complete clinical report variables in order to estimate the judged health status. Results: The use of 'patient's information' led to a better predictive ability in comparison with using only physiological parameters assessed by instruments. The complete set of variables (Patient+Instrumental) achieved 84% concordance, compared with 72% for the instrumental-only variables and 69% for the patient-only variables. The receiver operator characteristics curves graphically confirmed the described results. Conclusions: Patients have an active role in home monitoring, and their information appears relevant for a new telemedicine approach integrating subjective and objective vital signs. Combining patient information with instrumental parameters, it is possible to achieve a more correct automatic classification of health status of heart failure patients. [ABSTRACT FROM AUTHOR]

Summary: The cell-envelope of Mycobacterium tuberculosis plays a key role in bacterial virulence and antibiotic resistance. Little is known about the molecular mechanisms of regulation of cell-envelope formation. Here, we elucidate functional and structural properties of RNase AS, which modulates M. tuberculosis cell-envelope properties and strongly impacts bacterial virulence in vivo. The structure of RNase AS reveals a resemblance to RNase T from Escherichia coli, an RNase of the DEDD family involved in RNA maturation. We show that RNase AS acts as a 3′-5′-exoribonuclease that specifically hydrolyzes adenylate-containing RNA sequences. Also, crystal structures of complexes with AMP and UMP reveal the structural basis for the observed enzyme specificity. Notably, RNase AS shows a mechanism of substrate recruitment, based on the recognition of the hydrogen bond donor NH2 group of adenine. Our work opens a field for the design of drugs able to reduce bacterial virulence in vivo. [ABSTRACT FROM AUTHOR]

Physiological trade-offs mediated by limiting energy, resources or time constrain the simultaneous expression of major functions and can lead to the evolution of temporal separation between demanding activities. In birds, plumage renewal is a demanding activity, which accomplishes fundamental functions, such as allowing thermal insulation, aerodynamics and socio-sexual signaling. Feather renewal is a very expensive and disabling process, and molt is often partitioned from breeding and migration. However, trade-offs between feather renewal and breeding have been only sparsely studied. In barn swallows (Hirundo rustica) breeding in Italy and undergoing molt during wintering in sub-Saharan Africa, we studied this trade-off by removing a tail feather from a large sample of individuals and analyzing growth bar width, reflecting feather growth rate, and length of the growing replacement feather in relation to the stage in the breeding cycle at removal and clutch size. Growth bar width of females and length of the growing replacement feather of both sexes were smaller when the original feather had been removed after clutch initiation. Importantly, in females both growth bar width and replacement feather length were negatively predicted by clutch size, and more strongly so for large clutches and when feather removal occurred immediately after clutch completion. Hence, we found strong, coherent evidence for a trade-off between reproduction, and laying effort in particular, and the ability to generate new feathers. These results support the hypothesis that the derived condition of molting during wintering in long-distance migrants is maintained by the costs of overlapping breeding and molt. [ABSTRACT FROM AUTHOR]

Clostridium difficile is a Gram-positive bacterium and is the most commonly diagnosed cause of hospital-associated and antimicrobial-associated diarrhea. Despite the emergence of epidemic C. difficile strains having led to an increase in the incidence of the disease, a vaccine against this pathogen is not currently available. C. difficile strains produce two main toxins (TcdA and TcdB) and express three highly complex cell-surface polysaccharides (PSI, PSII and PSIII). PSII is the more abundantly expressed by most C. difficile ribotypes offering the opportunity of the development of a carbohydrate-based vaccine. In this paper, we evaluate the efficacy, in naive mice model, of PSII glycoconjugates where recombinant toxins A and B fragments (TcdA_B2 and TcdB_GT respectively) have been used as carriers. Both glycoconjugates elicited IgG titers anti-PSII although only the TcdB_GT conjugate induced a response comparable to that obtained with CRM197. Moreover, TcdA_B2 and TcdB_GT conjugated to PSII retained the ability to elicit IgG with neutralizing activity against the respective toxins. These results are a crucial proof of concept for the development of glycoconjugate vaccines against C. difficile infection (CDI) that combine different C. difficile antigens to potentially prevent bacterial colonization of the gut and neutralize toxin activity. [ABSTRACT FROM AUTHOR]

Abstract: The study was designed to investigate the effects of a new ophthalmic solution containing 0.05% vitamin B12 0.05% on corneal nerve regeneration in rats after corneal injury. Eyes of anesthetized male Wistar rats were subjected to corneal injury by removing the corneal epithelium with corneal brush (Algerbrush). After the epithelial debridement, the right eye of each animal received the instillation of one drop of the ophthalmic solution containing vitamin B12 0.05% plus taurine 0.5% and sodium hyaluronate 0.5% four time per day for 10 or 30 days. Left eyes were used as control and treated with solution containing taurine 0.5% and sodium hyaluronate 0.5% alone following the same regimen. Fluorescein staining by slit-lamp and morphological analysis was used to determine corneal wound healing. Immunohistochemistry, immunoblot and confocal microscopy were used to examine corneal re-innervation. Slit-lamp and histological analyses showed that re-epithelization of the corneas was accelerated in rats treated with vitamin B12. A clear-cut difference between the two groups of rats was seen after 10 days of treatment, whereas a near-to-complete re-epithelization was observed in both groups at 30 days. Vitamin B12 treatment had also a remarkable effect on corneal re-innervation, as shown by substantial increased in the expression of neurofilament 160 and β-III tubulin at both 10 and 30 days. The presence of SV2A-positive nerve endings suggests the presence of synapse-like specialized structures in corneal epithelium of the eye treated with vitamin B12. Our findings suggest that vitamin B12 treatment represents a powerful strategy to accelerate not only re-epithelization but also corneal re-innervation after mechanical injury. [Copyright &y& Elsevier]

Natal dispersal contributes to population dynamics and genetic structure. Individuals differ in whether or not they disperse and in the distance they travel from their natal site before settling to breed. Differences in natal dispersal are often associated with variation in other traits. These associations may arise because suites of morphological and behavioural traits are ultimately controlled by the same set of genes. The genes that control melanogenesis in vertebrates pleiotropically influence physiology and behaviour, including boldness and exploration. Because these personality traits predict dispersal, we tested the hypothesis that in the barn swallow, Hirundo rustica, melanic coloration predicts natal dispersal, using a solid matched case–control sampling design and a large sample. We found that males but not females with colour traits that reflect relatively more pheomelanic feather pigmentation were more likely to disperse, consistently with observations on the only other species for which dispersal in relation to plumage melanic coloration has so far been studied. To control for any confounding effects, we also analysed the association of dispersal with morphological traits and parasite infestation. Philopatric individuals were larger than dispersers, whereas dispersal strategy did not differ according to tail length, which is a sexually selected trait. Finally, philopatric females had a smaller infestation of a haematophagous louse fly. The present findings corroborate previous evidence that melanic coloration covaries with a suite of traits. In particular, they show that melanin-based plumage coloration predicts natal dispersal, independently of other factors also influencing dispersal. In addition, our results show that philopatric individuals were larger than dispersers possibly because individuals return to a benign natal place or because large body size confers an advantage in competitive interactions. Finally, they are compatible with the idea of host adaptation to local strains of a parasite with presumably small population size and low dispersing capacity. [Copyright &y& Elsevier]

Neisseria meningitidis is a major cause of bacterial meningitis worldwide, especially in the African meningitis belt, and has a high associated mortality. The meningococcal serogroups A, W, and X have been responsible for epidemics and almost all cases of meningococcal meningitis in the meningitis belt over the past 12 y. Currently no vaccine is available against meningococcal X (MenX). Because the development of a new vaccine through to licensure takes many years, this leaves Africa vulnerable to new epidemics of MenX meningitis at a time when the epidemiology of meningococcal meningitis on the continent is changing rapidly, following the recent introduction of a glycoconjugate vaccine against serogroup A. Here, we report the development of candidate glycoconjugate vaccines against MenX and preclinical data from their use in animal studies. Following optimization of growth conditions of our seed MenX strain for polysaccharide (PS) production, a scalable purification process was developed yielding high amounts of pure MenX PS. Different glycoconjugates were synthesized by coupling MenX oligosaccharides of varying chain length to CRM197 as carrier protein. Analytical methods were developed for in-process control and determination of purity and consistency of the vaccines. All conjugates induced high anti-MenX PS lgG titers in mice. Antibodies were strongly bactericidal against African MenX isolates. These findings support the further development of glycoconjugate vaccines against MenX and their assessment in clinical trials to produce a vaccine against the one cause of epidemic meningococcal meningitis that currently cannot be prevented by available vaccines. [ABSTRACT FROM AUTHOR]

Molt and ecdysis are costly activities crucial to several animals. Most birds completely molt their plumage once per year. The diverse energy and aerodynamic costs of molt are expected to shape the evolution of molt schedules and rate of feather renewal. Differences in molt strategies are also predicted between the sexes because of sex-related variation in fitness payoffs of rapid and early feather renewal. Feathers show barring patterns that reflect daily growth pulses. Ptilochronological analysis of growth bar width (GBW) reflecting condition-dependent feather growth rate can provide important, though overlooked information on molt strategies, and on the effects of body condition on feather renewal and subsequent migration or breeding. In this study of migratory Barn Swallows ( Hirundo rustica) wintering in Nigeria, for the first time we analyzed sex-related variation in molt schedules and feather growth rate using molecular sexing. We found no sex difference in molt schedules but faster feather growth in females. Hence, protandry in arrival of swallows to European breeding grounds does not depend on sex-specific timing of molt or feather renewal rate. Individuals with advanced molt had larger GBW and muscle mass, suggesting that individuals in good condition complete molt earlier thanks to faster feather growth. Arrival date on the breeding areas may thus reliably signal male quality, if molt completion constrains migration. Finally, the frequency of low GBW values among wintering males was larger than during breeding in swallows that winter in Nigeria, suggesting selection against low GBW. This study provides the first unequivocal data on sex-related variation in molt schedules in a species with no discrete sexual dimorphism, and emphasizes the potential of ptilochronology in ecological-evolutionary studies, as it shows that feather growth rate covaries with timing of molt but may not mediate protandrous migration. [ABSTRACT FROM AUTHOR]

Pigmentation of body surface in animals can have multiple determinants and accomplish diverse functions. Eumelanin and pheomelanin are the main animal pigments, being responsible of yellow, brownish-red and black hues, and have partly common biosynthetic pathways. Many populations of vertebrates show individual variation in melanism, putatively with large heritable component. Genes responsible for eu- or pheomelanogenesis have pleiotropic but contrasting effects on life-history traits, explaining the patterns of covariation observed between melanization and physiology (e.g. immunity and stress response), sexual behavior and other characters in diverse taxa. Yet, very few studies in the wild have investigated if eu- and pheomelanization predict major fitness traits like viability or fecundity. In this correlative study, by contrasting adult barn swallows (Hirundo rustica) matched for age, sex, breeding site, and year and date of sampling, we show that males but not females that survived until the next year had paler, relatively more eu- than pheomelanic pigmentation of ventral body feathers. Better performance of individuals that allocate relatively more to eumelanogenesis was expected based on previous evidence on covariation between eumelanic pigmentation and specific traits related to immunity and susceptibility to stress. However, together with the evidence of no covariation between viability and melanization among females, this finding raises the question of the mechanisms that maintain variation in genes for melanogenesis. We discuss the possibility that eu- and pheomelanization are under contrasting viability and sexual selection, as suggested by larger breeding and sperm competition success of darker males from other barn swallow subspecies. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study was to evaluate the role of a possible interaction between cannabinoid and muscarinic systems, both widely expressed in the ocular structure and involved in the control of bovine ciliary muscle contractility and intraocular pressure modulation. The ciliary muscle strips isolated by bovine eyes were exposed cumulatively to anandamide in the presence and in the absence of carbachol (5nM), in a miograph system for isometric recording. The experiments were also conducted in the presence of AM251 (100nM), 4-DAMP (100nM), Pertussis toxin (500ng/ml), U73122 (0.1 and 1μM), chelerythrine (1 and 10μM) and Y27632 (1 and 10μM). Contractile responses were expressed as the percentage of 10μM carbachol-induced contraction. The anandamide-induced contraction on bovine ciliary muscle strips was enhanced by the previous stimulation of Gq-protein-coupled muscarinic M3 receptors with carbachol. The contractile response to anandamide plus carbachol was affected by different inhibitors such as Pertussis toxin, phospholipase C, protein kinase C and Rho-kinase. The key results of the present study show that sequential activation of muscarinic M3 receptors and cannabinoid CB1 receptors produce synergistic contractile effects of the bovine ciliary muscle by involving the activation of Rho-kinase and protein kinase C. [Copyright &y& Elsevier]

Melanin is the main pigment in animal coloration and considerable variation in the concentrations of the two melanin forms (pheo- and eumlanin) in pigmented tissues exists among populations and individuals. Melanin-based coloration is receiving increasing attention particularly in socio-sexual communication contexts because the melanocortin system has been hypothesized to provide a mechanistic basis for covariation between coloration and fitness traits. However, with few notable exceptions, little detailed information is available on inter-individual and inter-population variation in melanin pigmentation and on its environmental, genetic and ontogenetic components. Here, we investigate melanin-based coloration in an Italian population of a passerine bird, the barn swallow (Hirundo rustica rustica), its sex- and age-related variation, and heritability. The concentrations of eu- and pheomelanin in the throat (brown) and belly (white-to-brownish) feathers differed between sexes but not according to age. The relative concentration of either melanin (Pheo:Eu) differed between sexes in throat but not in belly feathers, and the concentrations in males compared to females were larger in belly than in throat feathers. There were weak correlations between the concentrations of melanins within as well as among plumage regions. Coloration of belly feathers was predicted by the concentration of both melanins whereas coloration of throat feathers was only predicted by pheomelanin in females. In addition, Pheo:Eu predicted coloration of throat feathers in females and that of belly feathers in males. Finally, we found high heritability of color of throat feathers. Melanization was found to differ from that recorded in Hirundo rustica rustica from Scotland or from H. r. erythrogaster from North America. Hence, present results show that pigmentation strategies vary in a complex manner according to sex and plumage region, and also among geographical populations, potentially reflecting adaptation to different natural and sexual selection regimes, and that some coloration components seem to be highly heritable. [ABSTRACT FROM AUTHOR]

Sex ratio of adults (tertiary sex ratio, TSR) is a major feature of animal populations with consequences for their behaviour, genetic structure and viability. Spatial and temporal variation in TSR occurs within species but the mechanisms behind it are poorly understood. In this long-term study of a declining population of a socially monogamous, colonial, migratory bird, the barn swallow (Hirundo rustica), we first analyzed population-level variation in TSR ( = proportion of males) of yearlings at sexual maturation in relation to ecological conditions as gauged by annual survival rate of adults. TSR was male-biased both among yearlings and older individuals, but male bias of yearlings was more pronounced after years with larger decline in adult survival. Thus, male offspring were less susceptible to the adverse ecological conditions that cause increased mortality. Dispersal and settling site decisions can have major consequences on fitness via the effects of local TSR on mating and sperm competition. Breeding barn swallows are highly philopatric while natal dispersal is high and, together with mortality, is the main determinant of colony TSR. We thus also investigated the mechanisms of breeding colony choice by yearlings and found that TSR of new-settlers in a given colony and year was negatively predicted by TSR of returning, early arriving older individuals in that year, but not by overall TSR at the colony in the previous year. This suggests that in our male-biased population new-settler males respond to local TSR upon arrival to choose the sites with larger breeding opportunities. Hence, variation in ecological conditions as reflected by adult survival can shift the TSR of individuals recruiting into a local population, with potentially various demographic consequences. However, breeding site choice based on TSR tends to homogenize TSR at a population level likely by facilitating settling of dispersing males in colonies with less male-biased TSR. [ABSTRACT FROM AUTHOR]

The ecological conditions that a bird experiences during any stage of its life cycle may have consequences that become manifested at later life stages, and these 'carry-over effects' may be major components of variance in individual performance. Condition-dependent feather growth rate, as assessed by growth bars width (GBW), provides a unique, though largely under-exploited tool to investigate carry-over effects of ecological conditions and individual physiological state during molt. In this study of breeding barn swallows Hirundo rustica, which undergo a single complete annual molt of tail and wing feathers during wintering in sub-Saharan Africa, we first show that old (≥ 2 yr) females have larger GBW than old males and yearlings. GBW was smaller with larger infestations by common ectoparasites of barn swallows, independent of the swallows' age or sex, and larger GBW was associated with a higher index of body condition during the breeding season in males. Larger GBW predicted higher seasonal reproductive output of older males, but not reproductive output of younger males or females of any age class, with this higher reproductive output of older males mediated by higher offspring fledging success. However, no relationship with GBW was observed for seasonal reproductive output of males in the spring preceding the winter when the feathers were grown. Hence, this study suggests that the analysis of the rate of feathers growth ('ptilochronology') has a larger potential to serve as a powerful tool in the study of carry-over effects than has been appreciated to date. Specifically, the present results support the idea that conditions experienced during wintering in Africa and proximately reflected by GBW have carry-over effects on body condition and breeding success. These effects are sex and age specific, being more pronounced in older males, possibly as a consequence of differences in annual time routines and susceptibility to extrinsic factors among sex and age classes. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the effects of single and repeated intravitreal injections of bevacizumab on various retinal layers focusing more on retinal ganglion cells (RGCs) in healthy rats. Male Wistar rats were treated with intravitreal injection of bevacizimab (4μL) within right eye. Left eyes were injected with the same volume of balanced salt solution (BSS) and used as control. Ten rats received a single intravitreal injection and ten rats had three injections, with seven days time interval. Histological and immunohistochemical evaluations and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay were performed in order to find out if some degree of apoptosis could occur on RGCs. Histological and immunohistochemical analyses showed that bevacizumab induces neuronal loss compared to control eyes, after multiple injections. RGCs apoptosis after multiple treatments was demonstrated to occur by TUNEL, Annexin V and Bax assays. The loss of ganglion cells following repeated injections was confirmed and quantified by the decrease in RGC specific protein Brn3a measured by western blotting in ten additional rats. The present results need to be considered when multiple intravitreal injection of bevacizumab are performed to treat retinal diseases. [Copyright &y& Elsevier]

1. Longevity is a major determinant of individual differences in Darwinian fitness. Several studies have analyzed the stochastic, time-dependent causes of variation in longevity, but little information exists from free-ranging animal populations on the effects that environmental conditions and phenotype early in ontogeny have on duration of life. 2. In this long-term (1993-2011) study of a migratory, colonial, passerine bird, the barn swallow ( Hirundo rustica), we analyzed longevity and, in a subsample of individuals, lifetime reproductive success (LRS) of the offspring that reached sexual maturity in relation to hatching date, which can affect the rearing environment through a seasonal deterioration in ecological conditions. Moreover, we analyzed the consequences of variation in body size and, for the first time in any species, of a major component of immunity on longevity, both by looking at absolute phenotypic values and at deviations from the brood mean. 3. Accelerated failure time models showed that individuals of both sexes that hatched early in any breeding season enjoyed larger longevity and larger LRS, indicating directional selection for early breeding. Both male and female offspring with large T cell-mediated immune response relative to their siblings and female nestlings that dominated the brood size/age hierarchy had larger longevity than their siblings of inferior phenotypic quality/age. Conversely, absolute phenotypic values did not predict longevity. 4. Frailty modelling disclosed marked spatial heterogeneity in longevity among colonies of origin, again stressing the impact of rearing conditions on longevity. 5. This study therefore reinforces the notion that perinatal environment and maternal decisions over timing and site of breeding, and position in the brood hierarchy can have marked effects on progeny life history that extend well into adulthood. In addition, it provides the first evidence from any bird population in the wild that immune response when nestlings predicts individuals' longevity after sexual maturation. [ABSTRACT FROM AUTHOR]

Abstract: Endocannabinoids regulate vascular tone in a variety of vascular tissues. This study aimed to investigate the role of peroxisome proliferators-activated receptors (PPARs) in anandamide- and palmitoylethanolamide-induced relaxant responses on the bovine ophthalmic artery and to evaluate the mechanisms involved. The effects of anandamide and palmitoylethanolamide were examined under myographic conditions on arterial rings pharmacologically pre-contracted with 5-HT. Anandamide and palmitoylethanolamide relaxed the ophthalmic artery rings in time- and concentration-dependent manner stimulating the PPAR alpha (PPARα). The vasorelaxation to endocannabinoids was inhibited by PPARα antagonist GW6471 (1μM), but not the PPAR gamma (PPARγ) antagonist GW9662 (1μM). Anandamide-induced relaxation was attenuate during the first 60min by AM251, a selective antagonist of cannabinoid CB1 receptors, and Pertussis toxin, an inhibitor of Gi/o protein; by the contrast, the palmitoylethanolamide-induced vasorelaxation was unaffected by cannabinoid antagonists and Pertussis toxin. Endothelium removal decreases slightly the potency and efficacy to endocannabinoids. The relaxant effect to anandamide and palmitoylethanolamide was inhibited by L-NMMA (300μM), an inhibitor of nitric oxide synthase, and iberiotoxin (200nM), a selective blocker of large conductance Ca2+-activated K+ (BKCa). These data support the view that anandamide and palmitoylethanolamide relax the ophthalmic artery in a time-dependent manner via the transcription factors PPARα suggesting a function for them in the physiological mechanisms of vascular regulation. [Copyright &y& Elsevier]

Avian eggs are rich in carotenoids, which derive from maternal diet where they may be available in limiting amounts. Egg carotenoids may accomplish major roles in antioxidant protection or modulate physiological functions and growth, interfering with offspring redox status, potentially in a sex-dependent way. In this study of maternal effects in relation to sex and laying order of yellow-legged gull (Larus michahellis) chicks, we analyzed the consequences of increased yolk lutein concentration on plasma antioxidant capacity (AOC) and an index of early oxidative damage (reactive oxygen metabolites, ROM), till 9 days after hatching. To this end, for the first time we directly manipulated yolk lutein, thus avoiding any effect on other components of egg quality due to maternal supplementation before laying. Lutein did not increase AOC but increased ROM in males and in first-laid chicks. Hence, lutein did not act as an antioxidant and determined increased early oxidative damage, possibly because of upregulation of immune or other physiological functions, but these effects were sex-related and apparent in first-laid chicks with larger yolk lutein supply. ROM positively covaried with AOC, suggesting a trade-off between AOC and oxidative damage. Moreover, lutein injection altered the covariation between body size or immunity and AOC or ROM. Carotenoids may thus not be major antioxidants in birds and rather affect redox status by increasing oxidative damage in a sex-dependent way and interfere with the resolution of growth trade-offs. In the absence of sex-related allocation, maternal decisions on egg carotenoid concentration may depend on the balance between divergent effects on either sex. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: Autosomal dominant hypercholesterolemias are due to defects in the LDL receptor (LDLR) gene, in the apolipoprotein B-100 gene or in the proprotein convertase subtilisin/kexin type 9 gene. The aim of this study was to identify and functionally characterize mutations in the LDLR gene that account for most cases of familial hypercholesterolemia (FH). Methods: We enrolled 56 unrelated patients from Southern Italy with a clinical diagnosis of FH. The mutation screening was performed by direct sequencing of the promoter and the 18 exons of the LDLR gene and by multiplex ligation-dependent probe amplification (MLPA) analysis to search for large rearrangements. Results and conclusion: We found 5 new mutations, the causative role of which was demonstrated by functional characterization performed by quantification of fluorescent LDL uptake in EBV-transformed B lymphocytes. These results enlarge the spectrum of FH-causative LDLR mutations. Lastly, screening for large rearrangements is highly recommended for the genetic diagnosis of FH. [Copyright &y& Elsevier]

Abstract: A laminarin-diphtheria toxoid (CRM197) conjugate vaccine conferred protection against fungal infections in mice. We have now generated novel β-glucan-CRM197 vaccines, with either natural (Curd-CRM197) or synthetic linear (15mer-CRM197), or β-(1,6)-branched (17mer-CRM197) β-(1,3)-oligosaccharides, formulated with the human-acceptable adjuvant MF59. Curd-CRM197 and 15mer-CRM197 conjugates, which induced high titers of anti-β-(1,3)-glucan IgG, but no antibodies against β-(1,6)-glucan, conferred protection to mice lethally challenged with C. albicans. In contrast, the 17mer-CRM197 conjugate, which induced anti-β-(1,6)-glucan antibodies in addition to the anti-β-(1,3)-glucan IgG, was non-protective. These data provide some insights on β-glucan epitope(s) mediating antifungal protection and open the way to develop a synthetic oligosaccharide vaccine against fungal diseases. [Copyright &y& Elsevier]

Abstract: The present study investigates the direct action and the underlying mechanism(s) of epigallocatechin-3-gallate (EGCG) vasomotor effects on the bovine isolated ophthalmic artery. Adjacent rings were cut from each artery and mounted in a wire miograph system for isometric recording. Concentration–response curves for EGCG were constructed by adding cumulative concentrations of the drug to arterial rings pre-contracted with 5-HT (1 µM). Effects of mechanical endothelial cell removal and of selective blockers of the nitric oxide (NO)/cGMP pathways were investigated on the EGCG relaxant responses. EGCG relaxed ophthalmic arteries and maximum relaxation was 78.4±2.64%. Mechanical removal of endothelium, blockade of soluble guanylyl cyclase by 1H-1,2,4-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, 1 and 5 µM) or inhibition of nitric oxide (NO) synthase by N G-nitro-L-arginine (L-NAME, 50 and 100 µM) reduced significantly the relaxant response to catechin; moreover, the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 100 µM) significantly increased the vasorelaxant responses to EGCG. Relaxation to EGCG was inhibited by iberiotoxin (200 nM), a blocker of big-conductance Ca2+-activated K+ (BKCa) channel, whereas the blockade of KATP channel by glibenclamide (5 µM) and of small-conductance Ca2+-activated K+ (SKCa) channel by apamin (100 nM) elicited no effect. Interestingly, also inhibition of phosphoinositide-3-kinase (PI3K) by wortmannin (100 nM) and of Akt by SH6 (1 µM) markedly decreased the EGCG-evoked vasorelaxation. These data suggest that EGCG induced vasorelaxation in ophthalmic arteries with endothelium-intact via the activation of the NO/cGMP signalling pathway and defined an intriguing role for PI3K and Akt as upstream mediators for activation of NO-mediated relaxant responses. [Copyright &y& Elsevier]