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In the present paper we study the onset of the spin-induced scalarization of a Kerr black hole in scalar-Gauss–Bonnet gravity with a massive scalar field. Our approach is based on a ( 2 + 1 ) time evolution of the relevant linearized scalar field perturbation equation. We examine the region where the Kerr black hole becomes unstable giving rise to new scalarized rotating black holes with a massive scalar field. With increasing of the scalar field mass, the minimum value of the Gauss–Bonnet coupling parameter at which scalarization is possible, increases and thus the instability region shrinks. Interestingly, the introduction of scalar field mass does not change the critical minimal value of the black hole angular momentum a crit / M where the instability of the Kerr black hole develops.

The impact of male aging on male fertility has only recently become of interest to the scientific community. This study aims to assess the relationship between age and fertility among a sample of men, considering the individual and pathological characteristics. In this retrospective study data of semen analysis and medical history of 1294 Italian male patients were considered. Semen analysis was performed by light microscopy and transmission electron microscopy mathematically elaborated. A generalized linear model was used to explore the influence of male age on semen quality, considering as confounders wine consumption, smoking habits, presence of varicocele, consanguinity and positive semen bacteriological analysis and urethral swab. The mean age of the participants was 36.41 ± 6.379. Male aging without impact of confounders was correlated with a decrease in sperm concentration and motility and an increased in sperm necrosis. Sperm concentration and progressive motility were negatively related to the presence of confounders as wine consumption (sperm motility), urogenital infection (sperm concentration and motility), varicocele (sperm concentration) and consanguinity (sperm motility). Urogenital infection, varicocele and consanguinity positively correlated with sperm necrosis. The most important finding was the observation of a negative effect of male aging on sperm parameters such as concentration, motility, and viability. It is possible to hypothesize age-dependent changes of testicular environment, probably related to reactive oxygen species production. The demonstration, in a large sample of patients, that aging influences sperm quality strongly motivates further research focused on the mechanisms involved in this phenomenon and its effects on offspring fitness.

The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary conservation of gene expression and segmentation patterning between mammalian and amphibian nephrons, the Xenopus laevis pronephric kidney offers a simplified model for studying nephrogenesis. The Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes expression by forming multiprotein complexes with LIM binding protein 1 (Ldb1). However, few Lhx1-Ldb1 cofactors have been identified for kidney organogenesis. By tandem- affinity purification from kidney-induced Xenopus animal caps, we identified single-stranded DNA binding protein 2 (Ssbp2) interacts with the Ldb1–Lhx1 complex. Ssbp2 is expressed in the Xenopus pronephros, and knockdown prevents normal morphogenesis and differentiation of the glomus and the convoluted renal tubules. We demonstrate a role for a member of the Ssbp family in kidney organogenesis and provide evidence of a fundamental function for the Ldb1–Lhx1-Ssbp transcriptional complexes in embryonic development.

Summary The cytotoxicity of Au/Ag nanoparticles (NPs) on human spermatozoa was investigated in vitro. Semen from donors were incubated (37 °C, 60′–120′) with 30, 60, 125, 250 and 500 μM Au/Ag‐NPs. Sperm motility was evaluated following WHO guidelines; sperm viability was assessed with eosin Y test. Au‐NPs were characterised and localised with field emission gun‐based scanning transmission electron microscope/energy dispersive spectroscopy and transmission electron microscopy. Both tested NPs exerted a significant dose‐dependent effect on motility and viability of human spermatozoa (P < 0.001). Ag‐NPs seem to show a slightly elevated toxicity although not significant (P > 0.05). Au‐NPs were localised in spermatozoa, whereas Ag‐NPs were undetectable. In conclusion, Au‐NPs and Ag‐NPs do not appear to be harmful for human spermatozoa up to high concentrations (250–500 μM) that are probably difficult to reach in vivo. It is mandatory to explore the genotoxic effect of NPs in germ cells.

Summary Spermatozoa with a rare combination of two monomorphic sperm defects, dysplasia of the fibrous sheath (DFS) and alterations in head–mid‐piece junction were analysed. The main focus was to explore the status of the centriole, a key organisation during fertilisation, using the centrin 1, a calcium‐binding protein linked to this structure. The sperm quality was examined by light, scanning and transmission electron microscopy (SEM, TEM); immunocytochemistry was performed for tubulin, A‐kinase anchor protein 4 (AKAP4) and centrin 1. Spermatozoa showed DFS defect associated with anomalies in head–tail attachment detected by SEM and TEM. Immunolocalisation of tubulin, AKAP4 and centrin 1 confirmed these alterations. Centrin 1 was visible in 67% of spermatozoa (in only 13% centrin localised in a normal position); in the majority of sperm centrin 1's location was altered, sometimes bent; often four spots, indicating the presence of two implantation fossae, were detected. At the centriolar level, immunoreactive fragments, frequently invading the entire short and thick tail, were observed. Centrin 1 is an essential component of the spermatozoa connecting piece and plays a role in centrosome dynamics during sperm morphogenesis and in zygotes and early embryos during spindle assembly. It is important to shed light on these rare conditions in order to better manage the patients during assisted reproductive technology.

Summary The role of ghrelin and obestatin in male reproduction has not completely been clarified. We explored ghrelin and obestatin localisation in the male reproductive system. Polyclonal antibodies anti‐ghrelin and anti‐obestatin were used to detect the expression of these hormones in human testis, prostate and seminal vesicles by immunocytochemistry, while in ejaculated and swim up selected spermatozoa by immunofluorescence. Sertoli cells were positive for both peptides and Leydig cells for ghrelin; germ cells were negative for both hormones. Mild signals for ghrelin and obestatin were observed in rete testis; efferent ductules were the most immune reactive region for both peptides. Epididymis was moderately positive for ghrelin; vas deferens and seminal vesicles showed intense obestatin and moderate ghrelin labelling; prostate tissue expressed obestatin alone. Ejaculated and selected spermatozoa were positive for both peptides in different head and tail regions. This study confirms ghrelin localisation in Leydig and Sertoli cells; the finding that ghrelin is expressed in rete testis, epididymis, vas deferens and seminal vesicles is novel, as well as the localisation of obestatin in almost all tracts of the male reproductive system. This research could offer insights for stimulating other studies, particularly on the role of obestatin in sperm physiology, which is still obscure.

Almost 50% of infertility cases are associated with human male infertility. The sperm membrane is a key structure influencing sperm morphology and function in normal and pathological conditions. The fatty acid profile determines the performance not only of sperm motility but also of acrosomal reaction and sperm-oocyte fusion. This review presents available knowledge on the role of fatty acid composition in human sperm and spermatogenesis and discusses the influence of dietary fatty acids on the sperm fatty acid profile. Recent studies in biological sciences and clinical researches in this field are also reported. The topic object of this review has potential application in medicine by identifying potential causes of infertility.

We study possible observable images of a thin accretion disk around rotating hairy black holes with two non-trivial time-periodic scalar fields. Such black holes are a viable alternative to the Kerr black hole, having a much more complicated geodesic structure and resulting accretion disks. We investigate how the different amounts of scalar hair around the black holes, quantified by a normalized charge, alter the direct and indirect images of the disk. Our results show that for high values of this charge, close to a boson star limit, chaotic disk images are observed with multiple small, disconnected components. For moderately large amounts of scalar hair and corresponding normalized charge, although the images still exhibit chaotic behavior, a dominant central dark region component emerges. For lower values of the normalized charge, the accretion disk images qualitatively resemble those for the Kerr black hole.

Background Canakinumab is a human IgGκ monoclonal antibody targeting Interleukin (IL)-1β; its action involves the neutralization of the signaling of IL-1β, the most important cytokine in the pathogenesis of Osteoartrhitis (OA). In response to IL-1β, chondrocytes secrete other proinflammatory cytokines, neutral metalloproteinases (MMPs), nitric oxide (NO); furthermore IL-1β inhibits chondrocytes proliferation and induces apoptosis. Objectives The aim of our study was to evaluate the possible in vitro effects of canakinumab on human OA chondrocytes cultures cultivated in the presence or absence of tumor necrosis factor (TNF)-α. Methods Chondrocytes, from femoral cartilage of five OA patients who underwent surgery for hip prostheses, were isolated using sequential enzymatic digestion. Primary cultures so obtained were incubated with canakinumab (1μg/ml and 10μg/ml) alone or with TNF-α (10ng/ml). We evaluated after 48h cell viability, release of proteoglycans (PG) and NO in culture medium, inducible nitric oxide synthase (iNOS) and MMP-1,3,13 expression, the percentage of apoptosis and necrosis. After 24h we performed IL-1β dosage (ELISA). Finally, we used a transmission electron microscope (TEM) for morphological assessment. Results Canakinumab alone at the two concentrations studied hadn't cytotoxic effect and didn't modify significantly IL-1β levels in the culture medium. TNF-α caused a significant decrease of the percentage of viable cell (P<0.001) and a significant increase of IL-1β. Both concentrations of canakinumab significantly restored the cell viability and reduced IL-1β production in TNF-α stimulated chondrocytes. No significant modification of PG levels was observed in the cultures treated with canakinumab alone; TNF-α determined a significant decrease (P<0.001) in PG levels restored by canakinumab in a significant dose-dependent manner. Incubation of chondrocytes with canakinumab alone didn't affect nitrite release; TNF-α induced a significant increase (P<0.001) in NO production that was significantly (P<0.01) reduced after co-incubation with TNF-α and canakinumab at two concentrations used. The data of the NO were confirmed by the immunocytochemistry assay for iNOS. TNF-α stimulated chondrocytes displayed a significant increase of MMP-1,3,13 gene expression; a significant reduction was shown after co-treatment with TNF-α and canakinumab. Our experiments confirmed the pro-apoptotic effect of TNF-α and demonstrated a protective role of canakinumab at two concentrations examined. The biochemical results were further confirmed by TEM. Conclusions It is generally accepted that IL-1β and TNF-α are the pivotal cytokines involved in OA physiopathology. Hence, the neutralization of these cytokines appears to be a logical development for OA therapy. In the present study we showed, for the first time, that canakinumab counteracts the negative effect of TNF-α on OA chondrocyte cultures, probably inhibiting IL-1β signaling. References Dhimolea E. Mabs 2010;2:3-13. Fioravanti et al. J Pharmacol Sci 2012;20:6-14. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5066

Purpose Gonadotropins, interacting with their gonadal receptors, play a key role in sexual development, reproductive functions and metabolism. In this study we performed the genetic analysis of FSHR and LHR and semen investigation in 14 infertile men with normal level of T and elevated levels of FSH and/or LH in the absence of other causes of infertility. Methods Sperm parameters were analysed following WHO (2010) guidelines and sperm morphology by Transmission Electron Microscopy (TEM) analysis mathematically elaborated. FSHR and LHR gene mutations have been searched by PCR technique, followed by DHPLC analysis and direct sequencing. Results In FSHR, we found no difference in the frequency between Ala or Thr at position 307, Ser was at codon 680 in all subjects. Three patients had an heterozygous mutation at codon 419. Three intronic polymorphisms (rs2091787, rs6708637, rs1922464) were significantly found compared to controls; the single allele frequency and the odds ratio were calculated. Two new variants: the Cys338Arg and the Gln123Glu were detected in two different patients. Regarding LHR, three patients were heterozygous for the known variant Glu354Lys and two for Ile374Thr. Intronic polymorphisms were not identified. A new variant, the Val144Ile was found. By the routine semen analysis, variable seminal conditions in this group of patients was observed, on the contrary TEM data mathematically elaborated showed a homogeneous decrease in fertility index and increase in sperm pathologies such as apoptosis and immaturity. Conclusions The obtained results suggest that a deeper examination of spermatozoa, achieved by the use of more powerful tools such as TEM or molecular analysis, are advisable in patients with hypergonadotropic hypogonadism.