The regions of the sequence most exposed to the solvent within the amyloidogenic state of a protein initiate the aggregation process.

Formation of misfolded aggregates is an essential part of what proteins can do. The process of protein aggregation is central to many human diseases and any aggregating event needs to be prevented within a cell and in protein design. In order to aggregate, a protein needs to unfold its native state, at least partially. The conformational state that is prone to aggregate is difficult to study, due to its aggregating potential and heterogeneous nature. Here, we use a systematic approach of limited proteolysis, in combination with electrospray ionisation mass spectrometry, to investigate the regions that are most flexible and solvent-exposed within the native, ligand-bound and amyloidogenic states of muscle acylphosphatase (AcP), a protein previously shown to form amyloid fibrils in the presence of trifluoroethanol. Seven proteases with different degrees of specificity have been used for this purpose. Following exposure to the aggregating conditions, a number of sites along the sequence of AcP become susceptible to proteolytic digestion. The pattern of proteolytic cleavages obtained under these conditions is considerably different from that of the native and ligand-bound conformations and includes a portion within the N-terminal tail of the protein (residues 6-7), the region of the sequence 18-23 and the position 94 near the C terminus. There is a significant overlap between the regions of the sequence found to be solvent-exposed from the present study and those previously identified to be critical in the rate-determining steps of aggregation from protein engineering approaches. This indicates that a considerable degree of solvent exposure is a feature of the portions of a protein that initiate the process of aggregation

Heat Sensing Receptor TRPV1 Is a Mediator of Thermotaxis in Human Spermatozoa

The molecular bases of sperm thermotaxis, the temperature-oriented cell motility, are currently under investigation. Thermal perception relies on a subclass of the transient receptor potential [TRP] channels, whose member TRPV1 is acknowledged as the heat sensing receptor. Here we investigated the involvement of TRPV1 in human sperm thermotaxis. We obtained semen samples from 16 normozoospermic subjects attending an infertility survey programme, testis biopsies from 6 patients with testicular germ cell cancer and testis fine needle aspirates from 6 patients with obstructive azoospermia undergoing assisted reproductive technologies. Expression of TRPV1 mRNA was assessed by RT-PCR. Protein expression of TRPV1 was determined by western blot, flow cytometry and immunofluorescence. Sperm motility was assessed by Sperm Class Analyser. Acrosome reaction, apoptosis and intracellular-Ca2+ content were assessed by flow cytometry. We found that TRPV1 mRNA and protein were highly expressed in the testis, in both Sertoli cells and germ-line cells. Moreover, compared to no-gradient controls at 31°C or 37°C (Ctrl 31°C and Ctrl 37°C respectively), sperm migration towards a temperature gradient of 31-37°C (T gradient) in non-capacitated conditions selected a higher number of cells (14,9 ± 4,2×106 cells T gradient vs 5,1± 0,3×106 cells Ctrl 31°C and 5,71±0,74×106 cells Ctrl 37°C; P = 0,039). Capacitation amplified the migrating capability towards the T gradient. Sperms migrated towards the T gradient showed enriched levels of both TRPV1 protein and mRNA. In addition, sperm cells were able to migrate toward a gradient of capsaicin, a specific agonist of TRPV1, whilst capsazepine, a specific agonist of TRPV1, blocked this effect. Finally, capsazepine severely blunted migration towards T gradient without abolishing. These results suggest that TRPV1 may represent a facilitating mediator of sperm thermotaxis

Towards dense RGB-D visual odometry

LAUREA MAGISTRALEIn questa tesi presentiamo un sistema che stima il movimento di una singola telecamera RGB-D sfruttando il solo input video. Il sistema adopera la stima della posizione della telecamera per ricostruire tridimensionalmente la scena osservata, operando in real-time con un minimo ritardo. La parte principale del sistema è un "energy-based dense tracker". Il tracker minimizza una funzione obiettivo tentando di individuare la migliore trasformazione rigida che mappa un'immagine RGB-D su un'altra, sotto l'ipotesi di una scena statica osservata da una telecamera in movimento. La funzione obiettivo è definita come la combinazione lineare di una componente depthmap e una componente RGB. Noi proponiamo inoltre in questo elaborato una linearizzazione della funzione obiettivo che porta alla definizione di un sistema di equazioni in 6 incognite per le variabili rappresentanti il movimento della telecamera. Per permettere al sistema di tracciare movimenti ampi, risolviamo il sistema di equazioni in uno schema "coarse-to-fine". Variando i coefficienti della combinazione lineare delle due componenti della funzione obiettivo, possiamo spostare dinamicamente la priorità dalle caratteristiche strutturali nella depthmap alle caratteristiche di texture nell'immagine RGB. La posa stimata e la depthmap ad essa associata sono poi usate come input per un semplice sistema di ricostruzione tridimensionale che produce un modello denso del volume osservato. Il metodo di stima della posa della telecamera è stato applicato con successo a video catturati da telecamere portatili e generati sinteticamente. L'analisi quantitativa mostra che la nostra soluzione è più robusta a larghi movimenti della telecamera rispetto agli approcci RGB-D comunemente adottati, permettendo di effettuare odometria visuale con un minore numero di keyframes.We present a system that estimates the motion of a single moving RGB-D camera based on video input. The system operates in real-time with low delay and the motion estimates are used for 3D reconstruction purposes. The front end of the system is an energy-based dense tracker. The tracker minimizes an energy function which aims at finding the best rigid body motion to map one RGB-D image into another one under the assumption of a static scene filmed by the moving camera. Energy is defined as a linear combination of depthmap and RGB information. We then propose a linearization of the energy function which leads to a 6 x 6 normal equation for the twist coordinates representing the rigid body motion. To allow for larger motions, we solve this equation in a coarse-to-fine scheme. By varying the coefficients of the linear combination of the two energy components, we can dynamically shift focus from structure features in the depthmap to texture features in the RGB image. The estimated pose, together with the associated depth frame, is then used as input in a simple 3D reconstruction system which produces a dense model of the observed volume. The pose estimation method has been applied successfully to video recorded with handheld platforms and synthetically generated ones. Quantitative analysis shows that the solution is more robust to large camera motions than commonly adopted RGB-D approaches, allowing to perform visual odometry with a lower number of keyframes

Can Deep Learning Improve Technical Analysis of Forex Data to Predict Future Price Movements?

The foreign exchange market (Forex) is the world's largest market for trading foreign money, with a trading volume of over 5.1 trillion dollars per day. It is known to be very complicated and volatile. Technical analysis is the observation of past market movements with the aim of predicting future prices and dealing with the effects of market movements. A trading system is based on technical indicators derived from technical analysis. In our work, a complete trading system with a combination of trading rules on Forex time series data is developed and made available to the scientific community. The system is implemented in two phases: In the first phase, each trading rule, both the AI-based rule and the trading rules from the technical indicators, is tested for selection; in the second phase, profitable rules are selected among the qualified rules and combined. Training data is used in the training phase of the trading system. The proposed trading system was extensively trained and tested on historical data from 2010 to 2021. To determine the effectiveness of the proposed method, we also conducted experiments with datasets and methodologies used in recent work by Hernandez-Aguila et al., 2021 and by Munkhdalai et al., 2019. Our method outperforms all other methodologies for almost all Forex markets, with an average percentage gain of 20.2%. A particular focus was on training our AI-based rule with two different architectures: the first is a widely used convolutional network for image classification, i.e. ResNet50; the second is an attention-based network Vision Transformer (ViT). The results provide a clear answer to the main question that guided our research and which is the title of this paper

FSH Therapy in Male Factor Infertility: Evidence and Factors Which Might Predict the Response

Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10-18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as "non-responders". For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review's objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men

Communication of the diagnosis to Klinefelter subjects: an observational study on a key moment of the patient’s life

Purpose Klinefelter syndrome (KS) is the most prevalent sex chromosome disorder among males. The communication of the KS diagnosis holds significant implications for the diagnosis's acceptance. Recently, the increased use of prenatal diagnostic procedures has raised the question of whether, when, and by whom information, once provided to parents, should be communicated to their children/adolescents. Currently, there is limited information on this topic. This study aims to investigate the most suitable timing, content, and healthcare professionals (HCPs) according to KS patients' suggestions for conveying the diagnosis, analyzing the impact of communicating the KS diagnosis on patients and their reception of the communication in real-life situations. Furthermore, research entails a comparison of the actual communication and the patients' preferred mode of communication. Methods Self-reported interview data was collected from 196 adults diagnosed with KS. The interview was structured, consisting of 32 multiple-choice questions covering various areas related to diagnosis communication. Results Most patients with Klinefelter syndrome reported that earlier communication would have been beneficial. Communication before the age of 18 and by parents increased the likelihood of overcoming negative consequences and relying on psychological support. Conclusion To mitigate the adverse effects of poorly timed and inadequately delivered communication, typically by a single person, it is advisable that such communication be carried out at the onset of adolescence by an interdisciplinary team of HCPs (including psychologists, geneticists, endocrinologists) and parents. The information provided should not solely concentrate on hormonal and fertility aspects, but also consider other factors such as psychological variables

Parenting desire and intention in the health trajectories of transgender and gender diverse people: A systematic review

The present study aimed at systematizing the psychological contributions on parenting desires and intentions of transgender and gender diverse (TGD) individuals from a minority stress perspective and considering the cis-heteronormativity of our societies. A systematic search was conducted on February 2, 2024, in four databases: Scopus, PubMed, Web of Science, and PsycInfo. The inclusion criterion consisted of selecting peer-reviewed, indexed English articles specifically addressing the parenting desire and intention in TGD individuals. Thirty-nine records were included in the review, which highlighted that TGD individuals desire and/or intend to have children through a variety of ways (e.g., sexual intercourse, surrogacy, adoption, etc.). The findings are mixed in relation to various sociodemographic variables of the TGD population, which vary based on individual differences. Overall, hindrances due to fertility preservation and the scarce information provided, along with legislative policies prohibiting filiation and other ways to have children (e.g., adoption or surrogacy) to TGD people in various countries can render TGD people’s parenting desires and intentions unattainable phantasies. The reproductive path of TGD individuals is influenced by the cis-heteronormative norms of our society. Gender minority stress and resilience factors can have a significant impact on the TGD individuals’ desire or intention to have children