Spermatogenesis and Its Significance in Reproductive Medicine

As infertility rates across nations become a growing concern, the interest in the development of treatments, such as in vitro gametogenesis (IVG), increases. This is especially the case for male infertility. For instance, the average sperm count continues to decline across nations, while more adult and pediatric patients survive cancer only to be left with little to no options for fertility restorative therapies. Understanding the male reproductive system and the process of spermatogenesis, however, has proven to be a difficult task. Progress occurs slowly and inconsistencies remain in the literature while reports attempt to better understand spermatogonial stem cells (SSCs) in conjunction with spermatogenesis. Interestingly, stem cell behavior, the decision to self-renewal or commit to differentiation, has shown to be closely linked to the stem cell’s microenvironment (i.e. niche). Perhaps the missing pieces required to better understanding spermatogenesis are found in the re-defined perspective of SSC niche dynamics

Rejuvenation on the Road to Pluripotency

The technology of reprogramming differentiated cells into a pluripotent state, which can be used to derive virtually any cell type in vitro, has ignited the field of regenerative medicine. An equally revolutionary, but yet to be harnessed phenomenon, is the reset of age that occurs en route to pluripotency. This rejuvenation is clearly evident during reproduction, resulting in a young offspring from aged parental cells. Artificial reprogramming techniques built off this process, such as somatic cell nuclear transfer (SCNT) and induced pluripotent stem cell (iPSC) reprogramming techniques, are showing growing evidence for rejuvenation at the cellular level. These findings all points to an intimate relationship between reprogramming to pluripotency and the reset of age, and iPSC technology, especially, offers the possibility of a man‐made intervention in the aging process. Though in vitro cell reprogramming has been studied arguably for the last three decades, this application of specifically developing a protocol to rejuvenate cells, tissues, even whole organs has only just begun to be explored. There are still many challenges to realization but this technology has already famously shown that cell differentiation is more than a one‐way street, and, maybe, so is aging

The pricing of convertible bonds in the presence of structured conversion clauses: the case of Cashes

The aim of this paper is to analyse the pricing of highly structured convertible bonds by taking a real world case. To this end we examine the Cashes (Convertible And Subordinated Hybrid Equity-linked Securities), which are characterized by both voluntary and mandatory conversion that depend on different triggering events, as well as floating coupons whose payment hinges on dividends and earning of the issuer. Our results highlight that prices are very sensitive to the modelling of the sources of uncertainty, both market and credit risk, and underscore the relevance of the time horizon chosen for the estimation

Random geometric graphs in high dimension

Many machine learning algorithms used for dimensional reduction and manifold learning leverage on the computation of the nearest neighbours to each point of a dataset to perform their tasks. These proximity relations define a so-called geometric graph, where two nodes are linked if they are sufficiently close to each other. Random geometric graphs, where the positions of nodes are randomly generated in a subset of $\mathbb{R}^{d}$, offer a null model to study typical properties of datasets and of machine learning algorithms. Up to now, most of the literature focused on the characterization of low-dimensional random geometric graphs whereas typical datasets of interest in machine learning live in high-dimensional spaces ($d \gg 10^{2}$). In this work, we consider the infinite dimensions limit of hard and soft random geometric graphs and we show how to compute the average number of subgraphs of given finite size $k$, e.g. the average number of $k$-cliques. This analysis highlights that local observables display different behaviors depending on the chosen ensemble: soft random geometric graphs with continuous activation functions converge to the naive infinite dimensional limit provided by Erd\"os-R\'enyi graphs, whereas hard random geometric graphs can show systematic deviations from it. We present numerical evidence that our analytical insights, exact in infinite dimensions, provide a good approximation also for dimension $d\gtrsim10$

Smoking, health and ageing

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lecture of V. Nicita-Mauro on Smoking, health and ageing is summarized. Smoking represents an important ageing accelerator, both directly by triggering an inflammatory responses, and indirectly by favoring the occurrence of several diseases where smoking is a recognized risk factor. Hence, non-smokers can delay the appearance of diseases and of ageing process, so attaining longevity

Normal versus pathological cardiac fibroblast-derived extracellular matrix differentially modulates cardiosphere-derived cell paracrine properties and commitment

Human resident cardiac progenitor cells (CPCs) isolated as cardiosphere-derived cells (CDCs) are under clinical evaluation as a therapeutic product for cardiac regenerative medicine. Unfortunately, limited engraftment and differentiation potential of transplanted cells significantly hamper therapeutic success. Moreover, maladaptive remodelling of the extracellular matrix (ECM) during heart failure progression provides impaired biological and mechanical signals to cardiac cells, including CPCs. In this study, we aimed at investigating the differential effect on the phenotype of human CDCs of cardiac fibroblast-derived ECM substrates from healthy or diseased hearts, named, respectively, normal or pathological cardiogel (CG-N/P). After 7 days of culture, results show increased levels of cardiogenic gene expression (NKX2.5, CX43) on both decellularized cardiogels compared to control, while the proportion and staining patterns of GATA4, OCT4, NKX2.5, ACTA1, VIM, and CD90-positive CPCs were not affected, as assessed by immunofluorescence microscopy and flow cytometry analyses. Nonetheless, CDCs cultured on CG-N secreted significantly higher levels of osteopontin, FGF6, FGF7, NT-3, IGFBP4, and TIMP-2 compared to those cultured on CG-P, suggesting overall a reduced trophic and antiremodelling paracrine profile of CDCs when in contact with ECM from pathological cardiac fibroblasts. These results provide novel insights into the bidirectional interplay between cardiac ECM and CPCs, potentially affecting CPC biology and regenerative potential

A conservative discontinuous target volatility strategy

The asset management sector is constantly looking for a reliable investment strategy, which is able to keep its promises. One of the most used approaches is the target volatility strategy that combines a risky asset with a risk-free trying to maintain the portfolio volatility constant over time. Several analyses highlight that such target is fulfilled on average, but in periods of crisis, the portfolio still suffers market’s turmoils. In this paper, the authors introduce an innovative target volatility strategy: the discontinuous target volatility. Such approach turns out to be more conservative in high volatility periods. Moreover, the authors compare the adoption of the VIX Index as a risk measure instead of the classical standard deviation and show whether the former is better than the latter. In the last section, the authors also extend the analysis to remove the risk-free assumption and to include the correlation structure between two risky assets. Empirical results on a wide time span show the capability of the new proposed strategy to enhance the portfolio performance in terms of standard measures and according to stochastic dominance theory

Age-Related Modifications in Circulating IL-15 Levels in Humans

Aging is associated to a progressive establishing of a chronic inflammatory state linked to a continuous long exposure to antigens. Since IL-15 stimulates the proliferation of memory T cells and the immunosenescence is characterized by accumulation of memory T cells and exhaustion of naive T cells, we analyzed IL-15 levels in sera from 30 ultralongeval subjects with respect to those from young and old adults. IL-15 levels were assayed by immunoenzymatic methods. Ultralongeval subjects displayed significantly higher IL-15 levels with respect to both young and old controls. No statistical difference was found between old and young controls. These findings may explain, at least in part, the characteristic increase of memory cells in immunosenescence and the capacity of the immune system of centenarians to defend itself from infections through immune-inflammatory responses

Effect of levodopa on interleukin-15 and RANTES circulating levels in patients affected by Parkinson's disease.

Parkinson's disease (PD) is an extra-pyramidal neurodegenerative disorder, in which alterations of the immune system are involved. Interleukin (IL)-15 stimulates cellular immune response and induces growth and differentiation of various immune cells. RANTES, promoting leukocyte infiltration to sites of inflammation, mediates the trafficking and homing of immune cells. To clarify the potential effect of levodopa on the immunological network of PD, we analyzed IL-15 and RANTES serum levels in PD patients, treated or not with levodopa, and in healthy donors. Levodopa-treated patients showed significantly higher IL-15 and RANTES circulating levels with respect to healthy controls and higher, although not significantly, levels with respect to untreated patients. So, we hypothesize that the immunological alterations found in PD may be linked, at least in part, to levodopa therapy