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Understanding the impact of environmental and biological factors on species' habitat use is crucial for conservation. A regular presence of common bottlenose dolphins (Tursiops truncatus) has recently been observed in the Western Ligurian Sea, but their distribution, habitat preferences, and social dynamics remain poorly understood. This study aims to investigate these aspects, focusing on spatial distribution and habitat partitioning by age classes. Data were collected during 273 boat-based surveys from April 2018 to December 2021, resulting in 146 dolphin sightings. Group size and composition were analysed based on three group-types: N-groups including at least one newborn (n = 35), C-groups with at least one calf but no newborns (n = 62) and A-groups comprising only independent juveniles, subadults and/or adults (n = 49). Using an ensemble modelling approach (BIOMOD), each group's distribution was separately modelled incorporating seven environmental variables. Bathymetry, distance to the shelf break, bottom type and sea surface temperature emerged as the most significant predictors influencing groups' distribution. Results showed N-groups predominantly occupying areas further from the shore, C-groups distributed across both coastal waters and areas near the shelf break and A-groups principally found very close to shore. The study suggests habitat selection and group size vary based on the unique needs and threats faced by the different age classes. These insights are highly valuable for managing bottlenose dolphins in the Ligurian Sea, considering the area's particular morphology that leads to an important overlap between their presence and local anthropogenic activities. [ABSTRACT FROM AUTHOR]

Evolutionary game theory mathematically conceptualizes and analyzes biological interactions where one's fitness not only depends on one's own traits, but also on the traits of others. Typically, the individuals are not overtly rational and do not select, but rather inherit their traits. Cancer can be framed as such an evolutionary game, as it is composed of cells of heterogeneous types undergoing frequency-dependent selection. In this article, we first summarize existing works where evolutionary game theory has been employed in modeling cancer and improving its treatment. Some of these game-theoretic models suggest how one could anticipate and steer cancer's eco-evolutionary dynamics into states more desirable for the patient via evolutionary therapies. Such therapies offer great promise for increasing patient survival and decreasing drug toxicity, as demonstrated by some recent studies and clinical trials. We discuss clinical relevance of the existing game-theoretic models of cancer and its treatment, and opportunities for future applications. Moreover, we discuss the developments in cancer biology that are needed to better utilize the full potential of game-theoretic models. Ultimately, we demonstrate that viewing tumors with evolutionary game theory has medically useful implications that can inform and create a lockstep between empirical findings and mathematical modeling. We suggest that cancer progression is an evolutionary competition between different cell types and therefore needs to be viewed as an evolutionary game. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Bottlenose dolphin (Tursiops truncatus) habitat partitioning in relation to age classes in the northwest Mediterranean Sea." The original article contained an error in the author's names, which have now been corrected. The corrected article can be found online. The publisher, Springer Nature, remains neutral in terms of jurisdictional claims and institutional affiliations. The authors of the article are Elena Fontanesi, Davide Ascheri, Chiara Giulia Bertulli, Francesca Salvioli, and Niall McGinty. [Extracted from the article]

Fibroblast Growth Factor 21 (FGF21), Growth Differentiation Factor 15 (GDF15), and Humanin (HN) are mitochondrial stress-related mitokines, whose role in health and disease is still debated. In this study, we confirmed that their plasma levels are positively correlated with age in healthy subjects. However, when looking at patients with type 2 diabetes (T2D) or Alzheimer's disease (AD), two age-related diseases sharing a mitochondrial impairment, we found that GDF15 is elevated in T2D but not in AD and represents a risk factor for T2D complications, while FGF21 and HN are lower in AD but not in T2D. Moreover, FGF21 reaches the highest levels in centenarian' offspring, a model of successful aging. As a whole, these data indicate that (i) the adaptive mitokine response observed in healthy aging is lost in age-related diseases, (ii) a common expression pattern of mitokines does not emerge in T2D and AD, suggesting an unpredicted complexity and disease-specificity, and (iii) FGF21 emerges as a candidate marker of healthy aging. [ABSTRACT FROM AUTHOR]

A global reshaping of the immune responses occurs with ageing, indicated as immunosenescence, where mitochondria and mitochondrial metabolism play an important role. However, much less is known about the role of mitochondrial stress response in this reshaping and in particular of the molecules induced by such response, collectively indicated as mitokines. In this review, we summarize the current knowledge on the role of mitokines in modulating immune response and inflammation focusing on GDF15, FGF21 and humanin and their possible involvement in the chronic age-related low-grade inflammation dubbed inflammaging. Although many aspects of their biology are still controversial, available data suggest that these mitokines have an anti-inflammatory role and increase with age. Therefore, we hypothesize that they can be considered part of an adaptive and integrated immune-metabolic mechanism activated by mitochondrial dysfunction that acts within the framework of a larger anti-inflammatory network aimed at controlling both acute inflammation and inflammaging. [ABSTRACT FROM AUTHOR]

Aging is characterized by dynamic changes at metabolic level that lead to modifications in the composition of the metabolome. Since the identification of biomarkers that can discriminate people of different age and health status has recently attracted a great interest, we wondered whether age-specific changes in the metabolome could be identified and serve as new and informative biomarkers of aging and longevity. In the last few years, a specific branch of metabonomics devoted to the study of volatile organic compounds (VOCs) has been developed. To date, little is known about the profile of specific VOCs in healthy aging and longevity in humans; therefore, we investigated the profile of VOCs in both urine and feces samples from 73 volunteers of different age including centenarians that represent useful "super-controls" to identify potential biomarkers of successful aging and footprints of longevity. To this purpose, we performed a discriminant analysis by which we were able to identify specific profiles of urinary and fecal VOCs. Such profiles can discriminate different age groups, from young to centenarians, and, even more interesting, centenarians' offspring from age-matched controls. Moreover, we were able to identify VOCs that are specific for the couples "centenarians – offspring" or the trios "centenarians – offspring – spouse," suggesting the possible existence of a familiar component also for VOCs profile. [ABSTRACT FROM AUTHOR]

The examination of past and new chemical-isotopic data (2H/1H-18O/16O, 11B/10B and 87Sr/86Sr ratios) shows the meteoric origin of the Sawa Lake (Muthanna Governorate, Iraq) and its connection with the local aquifers, which feed the lake via the groundwater emerging from its floor through fault systems. The chemical and isotopic evaporation models are traced by geochemical computer codes by using a different composition of some potential inflows to the lake (e.g., the Euphrates River and Dammam aquifer). The main product of the chemical evaporation models is gypsum, as confirmed by the mineralogical examination of the sediment and the surrounding outcrops. A strong 18O-2H enrichment is a consequence of the evaporation effect in arid regions; δ18O-Cl models and δ11B = + 23.4‰ exclude the contribution of any seawater-derived fluids. This latter value along with 87Sr/86Sr = 0.707989 suggests a mixed origin from the Eocene-Miocene aquifers. The isotope and chemical evaporation paths from the meteorically recharged sources match the lake composition. However, compositional switches from NaCl toward MgCl2 occurred in the last decade and are related to post-drought periods, showing that the interaction of the recharging waters with the local soils (Na-Mg exchange and/or the leaching of the top layer salts) have a role in the chemical composition. This demonstrates that the lake is significantly influenced by climatic variations. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal (AM) fungi experience oxidative stress during the plant-fungal interaction, due to endogenous reactive oxygen species (ROS) produced by fungal metabolism and exogenous ROS produced by plant cells. Here, we examine the responses to HO in Gigaspora margarita, an AM fungus containing the endobacterial symbiont Candidatus Glomeribacter gigasporarum ( CaGg). Previous studies revealed that G. margarita with its endobacterium produces more ATP and has higher respiratory activity than a cured line that lacks the endobacterium. This higher bioenergetic potential leads to higher production of ROS and to a higher ROS-detoxifying capacity, suggesting a direct or indirect role of the endobacterium in modulating fungal antioxidant responses. To test the hypothesis that the fungal-endobacterial symbiosis may enhance the fitness of the AM fungus in the presence of oxidative stress, we treated the fungus with a sublethal concentration of HO and performed RNA-seq analysis. Our results demonstrate that (i) irrespective of the endobacterium presence, G. margarita faces oxidative stress by activating multiple metabolic processes (methionine oxidation, sulfur uptake, the pentose phosphate pathway, activation of ROS-scavenger genes); (ii) in the presence of its endobacterium, G. margarita upregulates some metabolic pathways, like chromatin status modifications and iron metabolism; and (iii) contrary to our hypothesis, the cured line responds to HO by activating the transcription of specific ROS scavengers. We confirmed the RNA-seq findings by measuring the glutathione and ascorbate concentration, which was the same in both lines after HO treatment. We conclude that both fungal lines may face oxidative stress, but they activate alternative strategies. [ABSTRACT FROM AUTHOR]

Grapevine, cultivated for both fruit and beverage production, represents one of the most economically important fruit crops worldwide. With the aim of better understanding how grape roots respond to beneficial microbes, a transcriptome sequencing experiment has been performed to evaluate the impact of a single arbuscular mycorrhizal (AM) fungal species ( Funneliformis mosseae) versus a mixed inoculum containing a bacterial and fungal consortium, including different AM species, on Richter 110 rootstock. Results showed that the impact of a single AM fungus and of a complex microbial inoculum on the grapevine transcriptome differed. After 3 months, roots exclusively were colonized after the F. mosseae treatment and several AM marker genes were found to be upregulated. The mixed inoculum led only to traces of colonization by AM fungi, but elicited an important transcriptional regulation. Additionally, the expression of genes belonging to categories such as nutrient transport, transcription factors, and cell wall-related genes was significantly altered in both treatments, but the exact genes affected differed in the two conditions. These findings advance our understanding about the impact of soil beneficial microbes on the root system of a woody plant, also offering the basis for novel approaches in grapevine cultivation. [ABSTRACT FROM AUTHOR]

Main conclusion: Systemic responses to an arbuscular mycorrhizal fungus reveal opposite phenological patterns in two tomato ripening mutants depending whether ethylene or light reception is involved. The availability of tomato ripening mutants has revealed many aspects of the genetics behind fleshy fruit ripening, plant hormones and light signal reception. Since previous analyses revealed that arbuscular mycorrhizal symbiosis influences tomato berry ripening, we wanted to test the hypothesis that an interplay might occur between root symbiosis and fruit ripening. With this aim, we screened seven tomato mutants affected in the ripening process for their responsiveness to the arbuscular mycorrhizal fungus Funneliformis mosseae. Following their phenological responses we selected two mutants for a deeper analysis: Green ripe ( Gr), deficient in fruit ethylene perception and high- pigment- 1 ( hp- 1), displaying enhanced light signal perception throughout the plant. We investigated the putative interactions between ripening processes, mycorrhizal establishment and systemic effects using biochemical and gene expression tools. Our experiments showed that both mutants, notwithstanding a normal mycorrhizal phenotype at root level, exhibit altered arbuscule functionality. Furthermore, in contrast to wild type, mycorrhization did not lead to a higher phosphate concentration in berries of both mutants. These results suggest that the mutations considered interfere with arbuscular mycorrhiza inducing systemic changes in plant phenology and fruits metabolism. We hypothesize a cross talk mechanism between AM and ripening processes that involves genes related to ethylene and light signaling. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the relationship between gastric emptying and demographic, clinical, histological, and secretory features in patients with nonautoimmune fundic atrophic gastritis. Only 31% of 45 patients with fundic atrophic gastritis presented with achlorhydria. Scintigraphic gastric emptying of solids was delayed compared to healthy controls. Patients with achlorhydria showed gastric emptying rates lower than those with preserved acid secretion. Significant, but weak, correlations were observed between emptying rates and both peak acid output (Rs = 0.33) and serum gastrin levels (Rs = -0.36), but not with grading of mucosal atrophy. No symptom differences were observed between patients with or without achlorhydria, but a weak correlation was detected between peak acid output and the severity of epigastric pain (Rs = 0.40). In conclusion, patients with fundic atrophic gastritis present delayed gastric emptying that is weakly related to the reduction of the acid secretion and the raising of serum gastrin levels rather than to the severity of the atrophy. [ABSTRACT FROM AUTHOR]

Sarcopenia, the progressive loss of muscle mass and strength, is a phenomenon characterizing human aging whose etiology is still not clear. While there is increasing evidence for the influence of inter-muscular adipose tissue infiltration in the development of sarcopenia, much less is known about a possible role for intra-muscular triglycerides (IMTG). IMTG accumulate in form of lipid droplets decorated by proteins such as Perilipins (Plins). In skeletal muscle the most abundant are Plin2 and Plin5. In this study we compared the expression of these two Plins in Vastus lateralis muscle samples of subjects of different age, both healthy donors (HD) and patients with limited lower limb mobility (LLMI). These latter are characterized by a condition of chronic physical inactivity. Plin2 expression resulted higher in old age for both HD and LLMI patients, while Plin5 slightly decreased only in LLMI patients. Moreover, in these patients, only Plin2 was associated with the decrease of muscle strength and the expression of factors related to muscle atrophy (MuRF1, Atrogin and p53). An increase in Plin2 and a concomitant decrease of Plin5 was also observed when we considered animal model of disuse-induced muscle atrophy. As a whole, these data indicate that Plin2 and Plin5 have a different expression pattern during muscle aging and inactivity, and only Plin2 appears to be associated with functional alterations of the muscle. [ABSTRACT FROM AUTHOR]

The Canan area (Honduras) is characterized by a gold-bearing ore deposit that is associated with quartz-veined shear zones. Gold mineralization occurs in low-to medium-grade metamorphic host-rocks (graphitic and sericitic schists). Hydrothermal fluids, which are associated with the emplacement of Cretaceous-Tertiary granodioritic intrusions, are responsible for the formation of quartz veins and the hydrothermal alteration of wall-rocks. Three main altered zones have been detected in the wall-rocks as far as 150 cm from the quartz veins. The distal zone (up to 50-cm thick) contains quartz, chlorite and illite. The intermediate zone is the thickest (up to 80 cm) and is marked by quartz, muscovite, sulphides, kaolinite and native elements such as Au and Ag. The proximal zone, which is close to the quartz veins, is rather thin (up to 25 cm) and contains clay minerals, Al-oxides-hydroxides and sulphides. The transition from the distal to the proximal zone is accompanied by the enrichment of SiO and the depletion of all other major elements, except for FeO. Precious metals occur in the highest concentrations in the intermediate zone (Au up to 7.6 ppm and Ag up to 11 ppm). We suggest that gold was transported as a reduced sulphur complex and was precipitated from the hydrothermal solution by the reaction of the sulphur complexes with Fe from the alteration of the mafic minerals of the host-rock. Fluid-wall-rock interactions seem to be the main cause of gold mineralization. Genetic relationships with a strike-slip fault system, hydrothermal alteration zones within the metamorphic wall-rocks, and an entire set of geochemical anomalies are consistent with orogenic-type gold deposits of the epizonal class. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal fungi (AMF) are important members of the plant microbiome. They are obligate biotrophs that colonize the roots of most land plants and enhance host nutrient acquisition. Many AMF themselves harbor endobacteria in their hyphae and spores. Two types of endobacteria are known in Glomeromycota: rod-shaped Gram-negative Candidatus Glomeribacter gigasporarum, CaGg, limited in distribution to members of the Gigasporaceae family, and coccoid Mollicutes-related endobacteria, Mre, widely distributed across different lineages of AMF. The goal of the present study is to investigate the patterns of distribution and coexistence of the two endosymbionts, CaGg and Mre, in spore samples of several strains of Gigaspora margarita. Based on previous observations, we hypothesized that some AMF could host populations of both endobacteria. To test this hypothesis, we performed an extensive investigation of both endosymbionts in G. margarita spores sampled from Cameroonian soils as well as in the Japanese G. margarita MAFF520054 isolate using different approaches (molecular phylotyping, electron microscopy, fluorescence in situ hybridization and quantitative real-time PCR). We found that a single AMF host can harbour both types of endobacteria, with Mre population being more abundant, variable and prone to recombination than the CaGg one. Both endosymbionts seem to retain their genetic and lifestyle peculiarities regardless of whether they colonize the host alone or together. These findings show for the first time that fungi support an intracellular bacterial microbiome, in which distinct types of endobacteria coexist in a single cell. [ABSTRACT FROM AUTHOR]

Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype-diabetes effect on insulin resistance evaluated by HOMA-IR ( p = 0.038). This result was mediated by variations in fasting plasma insulin ( p = 0.027), as no TP53 genotype-diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg ( p = 0.013) and Arg/Pro ( p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model-diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found ( p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene-diabetes interaction effects on fasting insulin ( β = −1.27; p = 0.001) and HOMA-IR ( β = −0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09-0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15-0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass. [ABSTRACT FROM AUTHOR]

Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands. [ABSTRACT FROM AUTHOR]

In the present work, we analyzed the survival features of six different Epstein-Barr virus (EBV)-stabilized lymphoid cell lines obtained from adult subjects and from subjects of more than 95 years. For the first, we found that lymphoid B cells from centenarians were more resistant to apoptosis induction and displayed a more developed lysosomal compartment, the most critical component of phagic machinery, in comparison with lymphoid B cells from adult subjects. In addition, cells from centenarians were capable of engulfing and digesting other cells, i.e., their siblings (even entire cells), whereas lymphoid cells from 'control samples', i.e., from adults, did not. This behavior was improved by nutrient deprivation but, strikingly, it was unaffected by the autophagy-modulating drug, rapamycin, an autophagy inducer, and 3-methyladenine, an autophagy inhibitor. Transcriptomic analyses indicated that: (1) aspartyl proteases, (2) cell surface molecules such as integrins and cadherins, and (3) some components of cytoskeletal network could contribute to establish this survival phenotype. Also, Kyoto Encyclopedia of Genes and Genomes pathways such as Wnt signaling pathway, an essential contributor to cell migration and actin cytoskeleton remodeling, appeared as prominent. Although we cannot rule out the possibility that EBV-immortalization could play a role, since we observed this phagic behavior in cells from centenarians but not in those from adults, we hypothesize that it may represent an important survival determinant in cells from centenarians. [ABSTRACT FROM AUTHOR]

As obligate symbionts of most land plants, arbuscular mycorrhizal fungi (AMF) have a crucial role in ecosystems, but to date, in the absence of genomic data, their adaptive biology remains elusive. In addition, endobacteria are found in their cytoplasm, the role of which is unknown. In order to investigate the function of the Gram-negative Candidatus Glomeribacter gigasporarum, an endobacterium of the AMF Gigaspora margarita, we sequenced its genome, leading to an ∼1.72-Mb assembly. Phylogenetic analyses placed Ca. G. gigasporarum in the Burkholderiaceae whereas metabolic network analyses clustered it with insect endobacteria. This positioning of Ca. G. gigasporarum among different bacterial classes reveals that it has undergone convergent evolution to adapt itself to intracellular lifestyle. The genome annotation of this mycorrhizal-fungal endobacterium has revealed an unexpected genetic mosaic where typical determinants of symbiotic, pathogenic and free-living bacteria are integrated in a reduced genome. Ca. G. gigasporarum is an aerobic microbe that depends on its host for carbon, phosphorus and nitrogen supply; it also expresses type II and type III secretion systems and synthesizes vitamin B12, antibiotics- and toxin-resistance molecules, which may contribute to the fungal host's ecological fitness. Ca. G. gigasporarum has an extreme dependence on its host for nutrients and energy, whereas the fungal host is itself an obligate biotroph that relies on a photosynthetic plant. Our work represents the first step towards unraveling a complex network of interphylum interactions, which is expected to have a previously unrecognized ecological impact. [ABSTRACT FROM AUTHOR]

At Jacupiranga (Brazil) the latest manifestations of C3 carbonatite are veins and impregnations of sövite composition containing carbonates, Fe-oxides, apatite, phlogopite, olivine, clinohumite, pyrochlore, zirconolite. Apatite contains fluid inclusions l.s. of two types: (i) two-phase fluid inclusions of complex composition (HO±CO±NaCl±KCl±NaHCO) with 17-50 vol.% of gas bubble, (ii) multi-phase melt inclusions of two types, carbonate-HO rich and silicate-carbonate-HO rich with very high homogenization temperatures up to 584°C and up to 1194°C, respectively. The coeval origin of fluid and melt inclusions allows to calculate the trapping pressures which indicate approximate depths of 30 to 60 km for the origin of the veins. Carbonatite veins contain Ba-poor tetra-ferriphlogopite of extreme composition which extends the compositional trend of the micas of Jacupiranga. The occurrence of zirconolite, Nb-rich pyrochlore and Ta-rich U-pyrochlore is mutually exclusive and related, probably, to the variation of fluorine content in the magmatic fluids. [ABSTRACT FROM AUTHOR]

Centenarians are exceptionally long living individuals who escaped the most common age-related diseases. In particular they appear to be effectively protected from cancers. The mechanisms that underlie this protection are quite complex and still largely unclear. To critically analyse the literature in order to propose a unifying hypothesis that can account for this cancer protection in centenarians. Review of the scientific literature regarding three main players in tumourigenesis such as IGF-1, inflammation and p53, and centenarians. Centenarians appear to be characterised by low IGF-1-mediated responses and high levels of anti-inflammatory cytokines such as IL-10 and TGF-β, a condition that results in protection from cancer. Both inflammation and IGF-1 pathway converge on the tumour suppressor p53. Accordingly, some studies indicate that genetic variants of p53 are associated with human longevity by providing protection from cancer mortality. The available data let us to hypothesise that among other possible mechanisms, well-preserved p53-mediated responses are likely a key factor contributing to protection from cancer in centenarians. [ABSTRACT FROM AUTHOR]

Immunosenescence features, such as thymic involution, alteration of T-cell repertoire, autoimmunity and accumulation of memory/effector T cells, may be the result, at least in part, of a zinc deficiency, which is often observed during ageing. Zinc, as essential trace element, affects the immune system function and it is an important regulator of apoptosis of immune cells. In this study we addressed the question whether zinc supplementation in vitro at physiological doses can affect spontaneous and oxidative stress-induced apoptosis in peripheral blood mononuclear cells from subjects of three different age groups: young (mean age 28 years), old (mean age 72 years) and nonagenarians. We studied different parameters related to apoptosis (phosphatydilserine exposure, mitochondrial membrane potential, caspase 3 cleavage) and we found that zinc, while decreasing spontaneous apoptosis, can increase oxidative stress-induced apoptosis in an age-related fashion, being this effect more evident in nonagenarians than in old or young subjects. In particular, zinc can increase late apoptosis/necrosis, a phenomenon that could trigger unnecessary inflammation in vivo. We surmise that these age-associated alterations in susceptibility to apoptosis may be due to a different effect of zinc on T cell subsets, that are altered in very old people, and finally that the zinc deficiency, which is often observed in aged subjects, could be a compensatory mechanism to counteract the inflammatory status of the elderly. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In healthy individuals, intraluminal lipids delay intestinal gas clearance, and this reflex is exaggerated in patients with irritable bowel syndrome (IBS). Our aim was to determine the site of action of abnormal lipid-induced reflexes in IBS. METHODS: In six patients with (IBS) predominantly complaining of bloating and in six healthy subjects, a mixture of gas (N2, O2, and CO2 in venous proportions to minimize diffusion) was infused (12 mL/min) either into the jejunum or into the ileum for 2 h, with simultaneous perfusion of lipids (0.5 kcal/min) into the proximal duodenum. Rectal gas evacuation was measured by a barostat. Abdominal perception (by a 0–6 scale) and girth changes were measured at 15-min intervals. The effects of jejunal versus ileal gas infusion were compared by paired tests in random order on separate days. RESULTS: IBS patients exhibited significant gas retention during infusion of gas into the jejunum (398 ± 90 mL vs−210 ± 105 mL in health, p < 0.05) but not during ileal infusion (−79 ± 87 mL vs−79 ± 78 mL in health, NS; p < 0.05 vs jejunal infusion). Gas retention during jejunal gas infusion in IBS patients was associated with significant abdominal distension (11 ± 3 mm girth increment vs 0 ± 1 mm during ileal gas infusion and 1 ± 1 mm in health, p < 0.05 for both) and abdominal symptoms (3.6 ± 0.6 score vs 2.6 ± 0.7 score during ileal gas infusion and 1.6 ± 0.5 score in health, p < 0.05 for both). CONCLUSIONS: In IBS patients intraluminal lipids impair intestinal gas clearance because of upregulated reflex inhibition of small bowel transit, without appreciable colonic effects. [ABSTRACT FROM AUTHOR]

A common arginine to proline polymorphism is harboured at codon 72 of the human p53 gene. In this investigation, we found that fibroblasts and lymphocytes isolated from arginine allele homozygote centenarians and sexagenarians (Arg+) undergo an oxidative-stress-induced apoptosis at a higher extent than cells obtained from proline allele carriers (Pro+). At variance, the difference in apoptosis susceptibility between Arg+ and Pro+ is not significant when cells from 30-year-old people are studied. Further, we found that Arg+ and Pro+ cells from centenarians differ in the constitutive levels of p53 protein and p53/MDM2 complex, as well as in the levels of oxidative stress-induced p53/Bcl-xL complex and mitochondria-localised p53. Consistently, all these differences are less evident in cells from 30-year-old people. Finally, we investigated the in vivo functional relevance of the p53 codon 72 genotype in a group of old patients (66-99 years of age) affected by acute myocardial ischaemia, a clinical condition in which in vivo cell death occurs. We found that Arg+ patients show increased levels of Troponin I and CK-MB, two serum markers that correlate with the extent of the ischaemic damage in comparison to Pro+ patients. In conclusion, these data suggest that p53 codon 72 polymorphism contributes to a genetically determined variability in apoptotic susceptibility among old people, which has a potentially relevant role in the context of an age-related pathologic condition, such as myocardial ischaemia.Cell Death and Differentiation (2004) 11, 962-973. doi:10.1038/sj.cdd.4401415 Published online 7 May 2004 [ABSTRACT FROM AUTHOR]

OBJECTIVES: Rectal compliance may influence rectal perception, but their functional implications remain incompletely understood. Our aim was to determine whether rectal function is related to bowel habit in the irritable bowel syndrome.METHODS: The responses to fixed tension rectal distension applied by means of a tensostat were compared among constipation-predominant (n= 9), diarrhea-predominant (n= 7), alternating habit (n= 11) irritable syndrome subgroups, and healthy controls (n= 15).RESULTS: Overall, patients had normal rectal compliance and increased perception, but compliance was lower in diarrhea-predominant as compared to constipation-predominant patients (6.7± 0.7 ml/mmHg vs. 9.9± 0.7 ml/mmHg, respectively;p<0.05) and perception was higher (39± 6 g vs. 64± 9 g tolerance, respectively;p<0.05).CONCLUSION: Distinctive tensosensitivity and compliance characterize rectal function in irritable bowel syndrome subgroups with different bowel habit. [ABSTRACT FROM AUTHOR]

The long forms of the dopamine D4 receptor ( DRD4) exon III repeat polymorphism ( L-DRD4) have been linked in some studies to the adult personality trait of novelty seeking (NS), as well as to infant personality traits related to interest and activity. The current investigation extends the results of our previous longitudinal study on 1- to 5-month-old neonates assessed by the Early and Revised Infancy Temperament Questionnaire (EITQ/RITQ), in which we found a significant correlation between the DRD4 polymorphism and the adaptability trait at 1 month of age. In this study, we examined the relationship between children′s behavior at 3 years of age, measured with the Toddler Temperament Scale (TTS), and DRD4 exon III repeat polymorphism. We found a significant association between the behavioral dimension of intensity of reaction and DRD4 genotypes. Current data failed to confirm the association with the adaptability trait. None of the extraversion and/or exploratory behavior measures was related to the L-DRD4 allele, as expected. In contrast, children with 4/7 genotypes showed worse response to new stimuli compared with 4/4 genotypes. This study corroborates only in part previous results on the link between the DRD4 gene and human temperament. [ABSTRACT FROM AUTHOR]

Summary ¶Fine- to coarse-grained plutonic nodules within the Petrazza pyroclastics (Paleo-Stromboli I period) consist of gabbroic rocks with variable amounts of interstitial material. They are characterised by cumulate textures and low pressure modal mineralogy formed by plagioclase (An96–87)+clinopyroxene (Mg-v 82–94)+olivine (Fo83–74)±amphibole±opaque minerals; the interstitial material consists of newly crystallised microlites (quenching) of plagioclase (An73–55)+amphibole+clinopyroxene±olivine±biotite±opaques and highly variable amounts of residual glasses that range in composition from shoshonite and high-K basaltic andesite to high-K andesite and latite. The interstitial material has a relatively high but variable degree of vesicularity. The whole rock incompatible element abundances are lower than – but the patterns are typical of – in subduction related magmas and the incompatible trace-elements are well correlated with the amount of the interstitial material. The Sr, Pb and Nd isotopic ratios resemble those of the extrusive rocks of Stromboli older series and the mineral chemistry of the gabbros is similar to that of the HKCA Paleo-Stromboli lavas. Modal mineralogy, mineral chemistry and chemical-isotopic whole rock compositions suggest that the cumulus portions of the gabbroic nodules crystallised from basaltic magmas compositionally compatible with those erupted by Stromboli volcano. The interstitial material does not represent the residual liquid after in situ crystallisation of the gabbros; it is also distinct from the juvenile host andesite magma. Textural evidence, Fe–Mg mineral/liquid partioning and mass balance calculations indicate that the interstitial material (quench crystals and vesicular glass) derived from infiltrated hydrous basaltic liquid undercooling and vesiculation of which occurred during the eruption of the Petrazza pyroclastics. [ABSTRACT FROM AUTHOR]

The onset of resistance to drug-induced apoptosis of tumour cells is a major problem in cancer therapy. We studied a drug-selected clone of promyelocytic HL-60 cells, called HCW-2, which display a complex resistance to a wide variety of apoptosis-inducing agents and we found that these cells show a dramatic increase in the expression of heat shock proteins (Hsps) 70 and 27, while the parental cell line does not. It is known that stress proteins such as Hsps can confer resistance to a variety of damaging agents other than heat shock, such as TNF- α, monocyte-induced cytoxicity, and also play a role in resistance to chemotherapy. This elevated expression of Hsps is paralleled by an increased activity of mitochondrial metabolism and pentose phosphate pathway, this latter leading to high levels of glucose-6-phosphate dehydrogenase and, consequently, of glutathione. Thus, the apoptotic-deficient phenotype is likely because of the presence of high levels of stress response proteins and GSH, which may confer resistance to apoptotic agents, including chemotherapic drugs. Moreover, the fact that in HCW-2 cells Hsp70 are mainly localised in mitochondria may account for the increased performances of mitochondrial metabolism. These observations could have some implications for the therapy of cancer, and for the design of combined strategies that act on antioxidant defences of the neoplastic cell. [ABSTRACT FROM AUTHOR]

Ganglionitis, i.e., the inflammatory neuropathy characterized by a marked lymphoplasmacellular infiltrate in the myenteric plexus, may underlie a variety of paraneoplastic, infectious, or neurological disorders, although occasional cases are idiopathic in origin. We report clinical, manometric, morphofunctional, and immunological features of three cases of idiopathic ganglionitis. All patients had megacolon and underwent surgery for repeated episodes of intestinal subocclusion. Esophageal, GI, and colonic manometry performed in one patient showed dysmotility of the whole gut. Histological examination of colonic and ileum specimens identified a prominent lymphoplasmacellular infiltrate within the myenteric plexus along with a marked decrease of a wide array of neuronal peptides/transmitters. In one patient, tissue analysis revealed progressive neuronal changes up to marked myenteric neuron damage. The inflammatory infiltrate in all patients comprised CD4+ and CD8+ T lymphocytes. Abundance of both subclasses of lymphocytes suggests that immune-mediated mechanisms were responsible for neuronal degeneration. In one patient, systemic steroid therapy brought a significant clinical improvement. The immunosuppressive approach deserves further investigation in patients with severe gut motor abnormalities attributable to idiopathic myenteric ganglionitis. [Copyright &y& Elsevier]

OBJECTIVE: Assessments of the pathophysiology of fecal incontinence are skewed toward anal sphincter function: however, rectal compliance, rectoanal sensation and capacity may also be relevant. The aim of this study was to evaluate the usual and some novel diagnostic approaches in fecal incontinence. METHODS: In 22 unselected patients with fecal incontinence (21 F, 33-75 yr), we quantified: 1) symptoms, anorectal manometry, and anal ultrasound; 2) anal perception of temperature and light touch; 3) rectal sensitivity and compliance to distension; and 4) rectal reservoir function. Control values were obtained from two groups of 11 (seven F, 32-53 yr), and 32 (18 F, 19-44 yr) volunteers. RESULTS: Patients had urge (14), passive (four), or combined (four) fecal incontinence; symptoms were mild in three, moderate in nine, and severe in 10 patients. Most had low sphincteric pressures and ultrasonic abnormalities. Temperature perception was impaired (p < 0.05) in incontinent patients, to a greater extent in the proximal anal canal and in patients with passive, as opposed to urge, incontinence. Intraluminal pressures for sensations of rectal distension were lower in incontinent patients (p = 0.02). Artificial stools elicited sensations of rectal filling at lower volumes than did a barostat bag, and in patients with urge, as opposed to passive, incontinence. In patients and controls, the sensation of urgency was associated (r² = 0.2, p < 0.01) with rectal compliance. CONCLUSIONS: We confirm that temperature sensation is impaired, and perception of rectal distension is not always reduced in fecal incontinence. Artificial stool tended to induce sensations at lower volumes than did balloon inflation. Altered sensory mechanisms may contribute to the pathophysiology of fecal incontinence. [ABSTRACT FROM AUTHOR]

We have examined the relationship between the common dopamine D4 receptor ( DRD4) exon III repeat polymorphism and infants' behavior measured with the Italian version of the Early and Revised Infancy Temperament Questionnaires (EITQ/RITQ) in 122 Italian neonates at 1 and 5 months of life, when the genetic contribution to the behavior can be more clearly assessed. Two-way (genotype × age) analysis of variance revealed a significant correlation with the temperamental subscale of adaptability [F(1, 120)=5.26, P<0.02]. At 1 month of life (early assessment), infants with long (L) DRD4 alleles presented significantly low scores (L 2.61±0.073; S 2.84+0.79; Newman-Keuls P=0.03) in comparison with the high scores of infants with short (S) alleles (L 2.4±0.059; S 2.25±0.57). These differences were not detected at 5 months of life (late assessment), denoting a strong environmental effect at this age on the genetic background. These results confirm and extend the genetic influence of the DRD4 gene in human temperament at birth. [ABSTRACT FROM AUTHOR]

Biomaterials, in particular those used for orthopaedic prostheses, consist of a metallic substrate, exhibiting excellent mechanical properties, coated with a ceramic layer, which guarantees resistance to the corrosion and an elevated bioactivity. In this paper the preparation of sol-gel films of hydroxyapatite, HA (Ca10(PO4)6(OH)2), on titanium substrate is described. The samples were obtained through the dip-coating method, starting from a colloidal suspension of hydroxyapatite. In order to increase the adhesion between the HA film and the metallic substrate, the same substrate has been preliminarily coated either with titanium oxide, TiO2 (in the anatase or rutile phase), or calcium titanate, CaTiO3 (perovskite). Also these latter films have been deposited from a sol-gel solution. The characterization of the films through XRD, SEM, and AFM gave good results for the crystallinity of the deposited HA; for what concerns the sample morphology, the films turned out to be homogeneous and crack-free. [ABSTRACT FROM AUTHOR]

The lysosomal degradation of several sphingolipids requires the presence of four small glycoproteins called saposins, generated by proteolytic processing of a common precursor, prosaposin. Saposins share several structural properties, including six similarly located cysteines forming three disulfide bridges with the same cysteine pairings. Recently it has been noted that also other proteins have the same polypeptide motif characterized by the similar location of six cysteines. These saposin-like (SAPLIP) proteins are surfactant protein B (SP-B), ‘Entamoeba histolytica’ poreforming peptide, NK-lysin, acid sphingomyelinase and acyloxyacyl hydrolase. The structural homology and the conserved disulfide bridges suggest for all SAPLIPs a common fold, called ‘saposin fold’. Up to now a precise fold, comprising five α-helices, has been established only for NK-lysin. Despite their similar structure each saposin promotes the degradation of specific sphingolipids in lysosomes, e.g. Sap B that of sulfatides and Sap C that of glucosylceramides. The different activities of the saposins must reside within the module of the α-helices and/or in additional specific regions of the molecule. It has been reported that saposins bind to lysosomal hydrolases and to several sphingolipids. Their structural and functional properties have been extensively reviewed and hypotheses regarding their molecular mechanisms of action have been proposed. Recent work of our group has evidenced a novel property of saposins: some of them undergo an acid-induced change in hydrophobicity that triggers their binding to phospholipid membranes. In this article we shortly review recent findings on the structure of saposins and on their interactions with lipids, with special attention to interactions with phospholipids. These findings offer a new approach for understanding the physiological role of saposins in lysosomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We performed a qualitative and quantitative analysis of the nitrinergic neurons in the esophageal and gastric component of the lower esophageal sphincter (LES) and gastric fundus of patients with primary achalasia. METHODS: Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and two from the gastric fundus of six patients with endstage achalasia who underwent an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the thoracic esophagus. Fixed sections were processed for NADPH-diaphorase histochemistry and the number (mean ± SE) of nitrinergic neurons per section was visually quantified in each specimen. RESULTS: In the controls, nitric oxide fibers were distributed to the muscle layer and surrounding myenteric neurons of both the LES and the gastric fundus. By contrast, achalasic patients showed a marked decrease of nitric oxide nerves and labeled neurons in both esophageal and gastric components of the LES and the gastric fundus. Quantitative assessment in achalasic patients showed that the mean number of nitrinergic neurons was dramatically reduced in both the esophageal (0.2 ± 0.1) and the gastric component (2 ± 0.6) of the LES as compared to those in controls (15 ± 5 and 12 ± 4, respectively; p < 0.05); nitrinergic neurons in the gastric fundus (3 ± 1) were significantly reduced in comparison to those of controls (10 ± 2) (p < 0.05). CONCLUSIONS: Our results indicate that achalasia is a motor disorder with an intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Dyspepsia is a common syndrome that often defies diagnosis. Whether the unexplained (or "functional") dyspepsia represents a homogeneous syndrome or includes different subgroups with specific clinical features has not been clarified. The aim of this study was to investigate the relationship between symptom severity, demographic features, and gastric dysmotility in a large series of patients with functional dyspepsia. METHODS: Severity of individual digestive symptoms, demographic features, and scintigraphic gastric emptying of solids were evaluated in 483 patients with chronic unexplained dyspepsia. RESULTS: Two main subgroups were identified. The first was characterized by predominant epigastric pain, male gender (61%), and normal gastric emptying. The second subgroup was characterized by predominant nonpainful symptoms, female gender (60%), a high frequency of associated irritable bowel syndrome (30%), and delayed gastric emptying (42%). A third group included approximately one-third of patients who did not present with any predominant symptom, and was characterized by a high frequency of delayed gastric emptying (30%), overlapping irritable bowel syndrome (28%), and gastroesophageal reflux disease (41%). CONCLUSIONS: Different subgroups exist among patients with functional dyspepsia seen in a referral center. They can be identified by the predominant symptom and are characterized by different demographic, clinical, and pathophysiological features. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Abnormalities of descending colon motility reported in a subset of patients with rectal evacuation disorders are consistent with a rectocolonic inhibitory reflex. Our aims were to evaluate distal colon motor function and rectal sensation in such patients and assess effects of biofeedback (BF) training on these functions. METHODS: Seven patients (five women, two men; mean age 36 yr) with rectal evacuation disorders were studied before and after 10-days biofeedback training; six healthy volunteers (five women, one man; mean age 30 yr) were studied once. Colonic compliance, motility, sensation thresholds, and perception scores during standardized rectal distentions were measured using two barostat-manometry assemblies inserted into the cleansed colon with the aid of flexible sigmoidoscopy. RESULTS: Sigmoid compliance, fasting, and postprandial motility index, and perception thresholds were similar in controls and patients before and after biofeedback training. Postprandial sigmoid tone tended (p = 0.09) to be lower in patients than controls; after biofeedback, postprandial tone was comparable to that in controls. Rectal urgency scores at 24 mm Hg distention were greater in patients than in controls (p = 0.02 for both). After biofeedback, there were trends for lower perceptions of urgency to defecate (7.6 ± 1.1 cm pre- vs 5.3 ± 1.5 post-; p = 0.04) at 24 mm Hg; conversely, gas sensation at 12 mm Hg was higher (1.2 ± 0.5 cm pre- vs 3.3 ± 0.6 post-; p = 0.05). CONCLUSIONS: Normalization of rectal evacuation and postprandial sigmoid tone in patients with evacuation disorders by biofeedback training supports the presence of a rectocolonic inhibitory reflex. Effect of biofeedback on rectal sensation in these patients requires further study. [ABSTRACT FROM AUTHOR]

Doppler ultrasound investigation of cerebral blood flow velocity was performed in hydrocephalic infants through the anterior fontanelle. Systolic (S) and end-diastolic (D) frequency values recorded on the anterior cerebral artery were used to define the pulsatility index (PI) calculated from the equation PI=S-D/S. Comparison between systolic, end-diastolic and pulsatility index values of 50 normal infants and 10 hydrocephalic infants showed a statistically significant difference ( P<0.05) for systolic and pulsatility index values. However, no significant difference was found for end-diastolic values. The authors believe that the phenomenon could be explained as an increase of the cerebrovascular compliance which counteracts the increase of the perivascular pressure in an attempt to maintain a normal cerebral blood flow. Therefore, the transfontanelle Doppler ultrasound technique may provide a useful and early tool in diagnosing cerebral blood-flow changesin hydrocephalic infants. [ABSTRACT FROM AUTHOR]

Craniopagus twinning is an extremely uncommon birth defect with an estimated incidence of 4-6 every 10 million births. The most complex and challenging issue is the feasibility of surgical separation, which involves not only technical but also socioethical problems and requires strict multidisciplinary cooperation between pediatricians, neuroradiologists, anesthesiologists, and plastic and neurological surgeons. The authors report a case in which separation was followed by the death of both twins and stress the importance, from the surgical and prognostic viewpoints, of the degree of vascular connections between the major dural sinuses, We propose a classification into three types according to severity. [ABSTRACT FROM AUTHOR]

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