Clusterin in neurological disorders: molecular perspectives and clinical relevance.

Firstly discovered in rete testis fluid, clusterin is a glycoprotein present in most of the other biological fluids. Several isoforms of clusterin are encoded from a single gene located on chromosome 8 in human species. Among the different isoforms, the secreted form of clusterin is expressed by a variety of tissues, including the nervous system under normal conditions. This form is presumed to play an anti-apoptotic role and seems to be a major determinant in cell survival and neuroplasticity after stroke. In animal models of this pathology, both neuronal and astroglial subpopulations express high levels of clusterin early after the ischemic damage. Recent lines of evidence point also to its possible involvement in neurodegenerative disorders. It is thought that in Alzheimer's disease the association between amyloidogenic peptides and clusterin contributes to limit Aβ species misfolding and facilitates their clearance from the extracellular space. Thus, intercellular and intracellular factors that modulate local clusterin expression in the nervous system may represent potent targets for neurodegenerative disease therapies. In this review we provide a critical overview of the most recent data on the involvement of clusterin in neurodegenerative diseases with special reference to their putative clinical relevance.

Evaluation qualitative de la compliance médicale [Qualitative evaluation of medical compliance].

OBJECTIVE: The effectiveness of CLP (Consultation and liaison psychiatry) interventions in a general hospital is difficult to evaluate; parameters potentially determinant as to effectiveness are numerous. Effectiveness evaluations are almost exclusively restricted to the duration of hospitalization. Since CLP may and often should be manifest beyond discharge, we intended to determine the agreement between our proposition and its execution as a measure of effectiveness. METHOD: We based our analyses principally on the general practitioner's appreciation of the CLP impact, a measure of effectiveness at distance from the consultation by a judge not directly involved in the consulting process. This qualitative assessment is based on a population of 50 patients. RESULTS: Our results suggest that agreement between our proposal and its complete execution is good concerning medication (90%) and referral rate after the hospitalization (85%), average as to liaison suggestions (65%) and clearly weak as to propositions regarding further investigations (< 30%). CONCLUSION: CLP proposals must be as close as possible to the in-patient physician's preoccupations to enhance the probability that they be executed. The concordance as to the proposal and its execution as well as the CLP impact estimation need be evaluated at distance. This evaluation must imply the general practitioner's assessment.

Oxidative and glycogenolytic cCapacities within the developing chick heart.

Cardiac morphogenesis and function are known to depend on both aerobic and anaerobic energy-producing pathways. However, the relative contribution of mitochondrial oxidation and glycogenolysis, as well as the determining factors of oxygen demand in the distinct chambers of the embryonic heart, remains to be investigated. Spontaneously beating hearts isolated from stage 11, 20, and 24HH chick embryos were maintained in vitro under controlled metabolic conditions. O(2) uptake and glycogenolytic rate were determined in atrium, ventricle, and conotruncus in the absence or presence of glucose. Oxidative capacity ranged from 0.2 to 0.5 nmol O(2)/(h.microg protein), did not depend on exogenous glucose, and was the highest in atria at stage 20HH. However, the highest reserves of oxidative capacity, assessed by mitochondrial uncoupling, were found at the youngest stage and in conotruncus, representing 75 to 130% of the control values. At stage 24HH, glycogenolysis in glucose-free medium was 0.22, 0.17, and 0.04 nmol glucose U(h.microg protein) in atrium, ventricle, and conotruncus, respectively. Mechanical loading of the ventricle increased its oxidative capacity by 62% without altering glycogenolysis or lactate production. Blockade of glycolysis by iodoacetate suppressed lactate production but modified neither O(2) nor glycogen consumption in substrate-free medium. These findings indicate that atrium is the cardiac chamber that best utilizes its oxidative and glycogenolytic capacities and that ventricular wall stretch represents an early and major determinant of the O(2) uptake. Moreover, the fact that O(2) and glycogen consumptions were not affected by inhibition of glyceraldehyde-3-phosphate dehydrogenase provides indirect evidence for an active glycerol-phosphate shuttle in the embryonic cardiomyocytes.

Tissue transglutaminase (TG2) acting as G protein protects hepatocytes against Fas-mediated cell death in mice.

Tissue transglutaminase (TG2) is a protein cross-linking enzyme known to be expressed by hepatocytes and to be induced during the in vivo hepatic apoptosis program. TG2 is also a G protein that mediates intracellular signaling by the alpha-1b-adrenergic receptor (AR) in liver cells. Fas/Fas ligand interaction plays a crucial role in various liver diseases, and administration of agonistic anti-Fas antibodies to mice causes both disseminated endothelial cell apoptosis and fulminant hepatic failure. Here we report that an intraperitoneal dose of anti-Fas antibodies, which is sublethal for wild-type mice, kills all the TG2 knock-out mice within 20 hours. Although TG2-/- thymocytes exposed to anti-Fas antibodies die at the same rate as wild-type mice, TG2-/- hepatocytes show increased sensitivity toward anti-Fas treatment both in vivo and in vitro, with no change in their cell surface expression of Fas, levels of FLIP(L) (FLICE-inhibitory protein), or the rate of I-kappaBalpha degradation, but a decrease in the Bcl-xL expression. We provide evidence that this is the consequence of the impaired AR signaling that normally regulates the levels of Bcl-xL in the liver. In conclusion, our data suggest the involvement of adrenergic signaling pathways in the hepatic regeneration program, in which Fas ligand-induced hepatocyte proliferation with a simultaneous inhibition of the Fas-death pathway plays a determinant role.

Eleven-year physical activity trends in a Swiss urban area.

OBJECTIVE: Regular physical activity is a major health determinant. Little is known about physical activity trends. We evaluated whether adult physical activity levels are changing in a Swiss urban state (Geneva). METHOD: We analyzed 11-year trends of physical activity indicators, including 3+MET-minutes per week and physical activity outside working hours, in population representative adults (n=9320, aged 35-74years, 50% women), relating declared physical activity to socioeconomic status, lifestyle, and clinical and blood markers. RESULTS: Combining yearly cohorts from 1999 to 2009, we found a significant trend for increased physical activity levels. Weekly age and sex adjusted 3+MET-minutes per week increased from 3023 to 3752, between 1999 and 2009 (P=0.02). The increase also concerned physical activity outside working hours (+18kcal/day/year). There was a shift from low levels of physical activity levels towards higher activities. Physical activity indicators were associated with socioeconomic status, comorbidities, and biological and anthropometric measures. The trend for increased physical activity was more prominent over the latter 5years. CONCLUSION: We found that physical activity levels have increased in an urban Swiss state. The increase is significant but small, and further efforts to promote physical activity are therefore warranted.

Uric acid transport and disease.

Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant properties that may be protective but can also be pro-oxidant, depending on its chemical microenvironment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hypertension, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metabolism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development.

VARIABILITY OF PHENOTYPIC, PROTEOMIC AND TRANSCRIPTOMIC EXPRESSION OF STAPHYLOCOCCUS AUREUS SURFACE ADHESINS

Staphylococcus aureus is a highly successful pathogen responsible of a wide variety of diseases, from minor skin infection to life-threatening sepsis or infective endocarditis, as well as food poisoning and toxic shock syndrome. This heterogeneity of infections and the ability of S. aureus to develop antibiotic-resistance to virtually any available drugs reflect its extraordinary capacity to adapt and survive in a great variety of environments. The pathogenesis of S. aureus infection involves a wide range of cell wall-associated adhesins and extracellular toxins that promote host colonization and invasion. In addition, S. aureus is extremely well equipped with regulatory systems that sense environmental conditions and respond by fine tuning the expression of metabolic and virulence determinants. Surface adhesins referred to MSCRAMMs - for Microbial Surface Component Recognizing Adherence Matrix Molecules - mediate binding to the host extracellular matrix or serum components, including fibrinogen, fibronectin, collagen and elastin, and promote tissue colonization and invasion. Major MSCRAMMs include a family of surface-attached proteins covalently bound to the cell wall peptidoglycan via a conserved LPXTG motif. Genomic analyses indicate that S. aureus contain up to 22 LPXTG surface proteins, which could potentially act individually or in synergy to promote infection. In the first part of this study we determined the range of adherence phenotypes to fibrinogen and fibronectin among 30 carriage isolates of S. aureus and compared it to the adherence phenotypes of 30 infective endocarditis and 30 blood culture isolates. Overall there were great variations in in vitro adherence, but no differences were observed between carriage and infection strains. We further determined the relation between in vitro adherence and in vivo infectivity in a rat model of experimental endocarditis, using 4 isolates that displayed either extremely low or high adherence phenotypes. Unexpectedly, no differences were observed between the in vivo infectivity of isolates that were poorly and highly adherent in vitro. We concluded that the natural variability of in vitro adherence to fibrinogen and fibronectin did not correlate with in vivo infectivity, and thus that pathogenic differences between various strains might only be expressed in in vivo conditions, but not in vitro. Therefore, considering the importance of adhesins expression for infection, direct measurement of those adhesins present on the bacterial surface were made by proteomic approach. 5 In the second series of experiments we assessed the physical presence of the LPXTG species at the staphylococcal surface, as measured at various time points during growth in different culture media. S. aureus Newman was grown in either tryptic soy broth (TSB) or in Roswell Park Memorial Institute (RPMI) culture medium, and samples were removed from early exponential growth phase to late stationary phase. Experiments were performed with mutants in the global accessory-gene regulator (agr), surface protein A (Spa) and clumping factor A (ClfA). Peptides of surface proteins were recovered by "trypsin-shaving" of live bacteria, and semi-quantitative proteomic analysis was performed by tandem liquid-chromatography and mass-spectrometry (LC-MS). We also determined in parallel the mRNA expression by microarrays analysis, as well as the phenotypic adherence of the bacteria to fibrinogen in vitro. The surface proteome was highly complex and contained numerous proteins theoretically not belonging to the bacterial envelope, including ribosomal proteins and metabolic enzymes. Sixteen of the 21 known LPXTG species were detected, but were differentially expressed. As expected, 9 known agr-regulated proteins (e.g. including Spa, FnBPA, ClfA, IsdA, IsdB, SasH, SasD, SasG and FmtB) increased up to the late exponential growth phase, and were abrogated in agr-negative mutants. However, only Spa and SasH modified their proteomic and mRNA profiles in parallel in the parent and its agr negative mutant, while all other LPXTG proteins modified their proteomic profiles independently of their mRNA. Moreover, ClfA became highly transcribed and active in in vitro fibrinogen adherence tests during late growth (24h), whereas it remained poorly detected by proteomics. Differential expression was also detected in iron-rich TSB versus iron-poor RPMI. Proteins from the iron-regulated surface determinant (isd) system, including IsdA, IsdB and IsdH were barely expressed in iron-rich TSB, whereas they increased their expression by >10 time in iron-poor RPMI. We conclude that semi-quantitative proteomic analysis of specific protein species is feasible in S. aureus and that proteomic, transcriptomic and adherence phenotypes demonstrated differential profiles in S. aureus. Furthermore, peptide signatures released by trypsin shaving suggested differential protein domain exposures in various environments, which might be relevant for antiadhesins vaccines. A comprehensive understanding of the S. aureus physiology should integrate all these approaches.

Education, disease prevalence and health service utilization in the Swiss National Health Survey "SOMIPOPS".

The relation among education, disease prevalence, and frequency of health service utilization was analyzed using data from the Swiss National Health Survey SOMIPOPS, conducted in 1981-1983 on a randomly selected sample of 4,255 individuals, representative of the entire Swiss population. The prevalence of several important cardiovascular, respiratory, digestive, osteoarticular, and psychiatric disorders was higher among less educated individuals; only allergic conditions were directly associated with indicators of social class. More educated individuals reported lower frequencies of general practitioner visits, but higher frequencies of specialized consultations. These findings confirm that education is an important determinant not only of mortality but also of morbidity and health-care utilization and require careful consideration in terms of the planning and evaluation of health services.

Prediction of postnatal outcome in fetuses with pulmonary hypoplasia by fetal-MRI: Comparison between lung volumetry and pulmonary signal intensity values

Purpose: Pulmonary hypoplasia is a determinant parameter for extra-uterine life. In the last years, MRI appears as a complement to US in order to evaluate the degree of pulmonary hypoplasia in foetuses with congenital anomalies, by using different methods - fetal lung volumetry (FLV), lung-to-liver signal intensity ratio (LLSIR)-. But until now, information about the correlation between the MRI prediction and the real postnatal outcome is limited. Methods and materials: We retrospectively reviewed the fetal MRI performed at our Institution in the last 8 years and selected the cases with suspicion of fetal pulmonary hypoplasia (n = 30). The pulmonary volumetry data of these foetuses were collected and the lung-to-liver signal intensity ratio (LLSIR) measures performed. These data were compared with those obtained from a control group of 25 foetuses considered as normal at MRI. The data of the study group were also correlated with the autopsy records or the post-natal clinical information of the patients. Results: As expected, the control group showed higher FLV and LLSIR values than the problem group at all gestational ages. Higher values of FLV and LLSIR were associated with a better post-natal outcome. Sensitivity, specificity, positive and negative predictive values and accuracy for the relative LLSIR and the relative FLV showed no significant differences. Conclusion: Our data show that not only the FLV but also the relative LLSIR inform about the degree of fetal lung development. This information may help to predict the fetal outcome and to evaluate the need for neonatal intensive care.

Impact of colonic cleansing on quality and diagnostic yield of colonoscopy: the European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study.

BACKGROUND: The quality of colon cleansing is a major determinant of quality of colonoscopy. To our knowledge, the impact of bowel preparation on the quality of colonoscopy has not been assessed prospectively in a large multicenter study. Therefore, this study assessed the factors that determine colon-cleansing quality and the impact of cleansing quality on the technical performance and diagnostic yield of colonoscopy. METHODS: Twenty-one centers from 11 countries participated in this prospective observational study. Colon-cleansing quality was assessed on a 5-point scale and was categorized on 3 levels. The clinical indication for colonoscopy, diagnoses, and technical parameters related to colonoscopy were recorded. RESULTS: A total of 5832 patients were included in the study (48.7% men, mean age 57.6 [15.9] years). Cleansing quality was lower in elderly patients and in patients in the hospital. Procedures in poorly prepared patients were longer, more difficult, and more often incomplete. The detection of polyps of any size depended on cleansing quality: odds ratio (OR) 1.73: 95% confidence interval (CI)[1.28, 2.36] for intermediate-quality compared with low-quality preparation; and OR 1.46: 95% CI[1.11, 1.93] for high-quality compared with low-quality preparation. For polyps >10 mm in size, corresponding ORs were 1.0 for low-quality cleansing, OR 1.83: 95% CI[1.11, 3.05] for intermediate-quality cleansing, and OR 1.72: 95% CI[1.11, 2.67] for high-quality cleansing. Cancers were not detected less frequently in the case of poor preparation. CONCLUSIONS: Cleansing quality critically determines quality, difficulty, speed, and completeness of colonoscopy, and is lower in hospitalized patients and patients with higher levels of comorbid conditions. The proportion of patients who undergo polypectomy increases with higher cleansing quality, whereas colon cancer detection does not seem to critically depend on the quality of bowel preparation.

A new way of quantifying dominant upper-limb mobility in healthy and painful shoulders

Introduction: Quantification of daily upper-limb activity is determinant in the evaluation of shoulder surgery. For a number of shoulder diseases, roblems in performing daily activities have been expressed in terms of upper-limb usage. Althought many instruments measure upper-limb movements, there is no accepted standard or widely used objective measure and no device to differenciate left or right shoulder usage. We present an objective method to measure the mobility and quantify the usage of dominant and healthy or painfull shoulder movement during daily life. Methods: 12 patients with unilateral pathological shoulder (rotator cuff disease) are compared to 18 control subjects (10 right and 8 left handed). Both SST and DASH questionnaires were completed by each one. Three inertial miniature modules including triaxial gyroscopes and accelerometers were fixed on the dorsal side of both humerus, and on the thorax. An ambulatory datalogger have recorded the signals during one day. Results: We observed that right handed healthy subjects used 18% and 26% more their dominant shoulder during respectively stand and sit postures while left handed subjects used 8% and 18% more their left side. In walking periods, shoulder mobility was quite alike for both sides. Patients affected on their dominant arm (PD group) mostly used their non-dominant side (respectively 5% and 9% during stand and sit). For the patients affected on their non-dominant shoulder (PND group), this difference is respectively 28% and 26%. Moreover, we can note that, during walking periods, a difference can be observed (on the contrary to controls). Patients used 13% and 15% more their nonpathologic side respectively for PD and PND groups. Conclusion: Inertial sensors, during long-term ambulatory monitoring of upper limbs, can quantify the difference between dominant and nondominant sides. Patients used more their non affected shoulder during daily life. For the PD group, the difference with control can be shown during walking. These results are very encouraging for future evaluation of patients with shoulder injuries since it can provide an objective evaluation of the shoulder mobility and of the treatment outcome during daily life.

Asking about adherence - from flipping the coin to strong evidence.

In the era of antiretroviral therapy (ART) as prevention for transmission of HIV as well as treatment for HIV-positive individuals irrespective of CD4 cell counts, the importance of adherence has grown. Although adherence is not the only determinant of treatment success, it is one of the only modifiable risk factors. Treatment failure reduces future treatment options and therefore long-term clinical success as well as increases the possibility of developing drug resistant mutations. Drug-resistant strains of HIV can then be transmitted to uninfected or drug-naïve individuals limiting their future treatment options, making adherence an important public-health topic, especially in resource-limited settings. Adherence should be monitored as a part of routine clinical care; however, no gold standard for assessment of adherence exists. For use in daily clinical practice, self-report is the most likely candidate for widespread use due to its many advantages over other measurement methods, such as low cost and ease of administration. Asking individuals about their adherence behaviour has been shown to yield valid and predictive data - well beyond the mere flip of a coin. However, there is still work to be done. This article reviews the literature and evidence on self-reported adherence, identifies gaps in adherence research, and makes recommendations for clinicians on how to best utilise self-reported adherence data to support patients in daily clinical practice.

Neurally adjusted ventilatory assist can improve arterial oxygenation

INTRODUCTION. Neurally Adjusted Ventilatory Assist (NAVA) [1] is a new spontaneousassisted ventilatory mode which uses the diaphragmatic electrical activity (Eadi) to pilot the ventilator. Eadi is used to initiate the ventilator's pressurization and cycling off. Delivered inspiratory assistance is proportional to Eadi. NAVA can improve patient-ventilator synchrony [2] compared to pressure support (PS), but little is known about its effect on minute ventilation and oxygenation. OBJECTIVES. To compare the effects of NAVA and PS on minute ventilation and oxygenation and to analyze potential determinant factors for oxygenation. METHODS. Comparison between two 20-min periods under NAVA and PS. NAVA gain (proportionality factor between Eadi and delivered pressure) set as to obtain the same peak pressure as in PS. FIO2 and positive end-expiratory pressure (PEEP) were the same in NAVA and PS. Blood gas analyses were performed at the end of both recording periods. Statistical analysis: groups were compared with paired t tests or non parametric Wilcoxon signed-rank tests. p\0.05 was considered significant. RESULTS. [Mean ± SD]: 22 patients (age 66 ± 12 year, 7 M/15F, BMI 23.4 ± 3.1 kg/m2), 8 patients with COPD. Initial settings: PS 13 ± 3 cmH2O, PEEP 7 ± 2 cmH2O, NAVA gain 2.2 ± 1.8. Minute ventilation and PaCO2 were the same with both modes (p = 0.296 and 0.848, respectively). Tidal volume was lower with NAVA (427 ± 102 vs. 477 ± 102 ml, p\0.001). In contrast respiratory rate was higher with NAVA (25.6 ± 9.5 vs. 22.3 ± 8.9 cycles/min). Arterial oxygenation was improved with NAVA (PaO2 85.1 ± 28.9 vs. 75.8 ± 11.9 mmHg, p = 0.017, PaO2/FIO2 210 ± 53 vs. 195 ± 58 mmHg, p = 0.019). Neural inspiratory time (Tin) was comparable between NAVA and PS (p = 0.566). Among potential determinant factors for oxygenation, mean airway pressure (Pmean) was lower with NAVA (10.6 ± 2.6 vs. 11.1 ± 2.4 cmH2O, p = 0.006), as was the pressure time product (PTP) (6.8 ± 3.0 vs. 9.2 ± 3.5 cmH2O 9 s, p = 0.004). There were less asynchrony events with NAVA (2.3 ± 2.0 vs. 4.4 ± 3.8, p = 0.009).Tidal volume variability was higher with NAVA (variation coefficient: 30 ± 19.5 vs. 13.5 ± 8.6, p\0.001). Inspiratory time in excess (Tiex) was lower with NAVA (56 ± 23 vs. 202 ± 200 ms, p = 0.001). CONCLUSION. Despite lower Pmean and PTP in NAVA, arterial oxygenation was improved compared to PS. As asynchronies may be associated with an increased work of breathing and a higher oxygen consumption, their decrease in number with NAVA could be an explanation for oxygenation improvement. Another explanation could be the increase in VT variability. Further studies should now be performed to confirm the potential of NAVA in improving arterial oxygenation and explore the underlying mechanisms.

How T cell receptors interact with peptide-MHCs: A multiple steered molecular dynamics study.

The T-cell receptor (TCR) interaction with antigenic peptides (p) presented by the major histocompatibility complex (MHC) molecule is a key determinant of immune response. In addition, TCR-pMHC interactions offer examples of features more generally pertaining to protein-protein recognition: subtle specificity and cross-reactivity. Despite their importance, molecular details determining the TCR-pMHC binding remain unsolved. However, molecular simulation provides the opportunity to investigate some of these aspects. In this study, we perform extensive equilibrium and steered molecular dynamics simulations to study the unbinding of three TCR-pMHC complexes. As a function of the dissociation reaction coordinate, we are able to obtain converged H-bond counts and energy decompositions at different levels of detail, ranging from the full proteins, to separate residues and water molecules, down to single atoms at the interface. Many observed features do not support a previously proposed two-step model for TCR recognition. Our results also provide keys to interpret experimental point-mutation results. We highlight the role of water both in terms of interface resolvation and of water molecules trapped in the bound complex. Importantly, we illustrate how two TCRs with similar reactivity and structures can have essentially different binding strategies. Proteins 2011; © 2011 Wiley-Liss, Inc.

Evaluation of an online, case-based interactive approach to teaching pathophysiology

Rapport de synthèse : L'article qui fait l'objet de ma thèse évalue une nouvelle approche pédagogique pour l'apprentissage de certains chapitres de physiopathologie. Le dispositif pédagogique se base sur l'alternance d'apprentissage ex-cathedra et de l'utilisation d'un site web comprenant des vignettes cliniques. Lors de la consultation de ces-dernières, l'étudiant est invité à demander des examens de laboratoire dont il pourrait justifier la pertinence selon le cas clinique étudié. La nouveauté du procédé réside dans le fait que, préalablement à son cours ex-cathedra, l'enseignant peut consulter les statistiques de demandes de laboratoire et ainsi orienter son cours selon les éléments mal compris par les étudiants. A la suite du cours ex-cathedra, les étudiants peuvent consulter sur internet la vignette clinique complète avec des explications. A l'issue de tout le cours, une évaluation auprès des étudiants a été conduite. Le procédé a été mis en place durant deux années consécutives et l'article en discute notamment les résultats. Nous avons pu conclure que cette méthode innovatrice d'enseignement amène les étudiants à mieux se préparer pour les cours ex-cathedra tout en permettant à l'enseignant d'identifier plus précisément quelles thématiques étaient difficiles pour les étudiants et donc d'ajuster au mieux son cours. Mon travail de thèse a consisté à créer ce dispositif d'apprentissage, à créer l'application web des vignettes cliniques et à l'implanter durant deux années consécutives. J'ai ensuite analysé les données des évaluations et écrit l'article que j'ai présenté à la revue 'Medical Teacher'. Après quelques corrections et précisions demandées par le comité de lecture, l'article a été accepté et publié. Ce travail a débouché sur une seconde version de l'application web qui est actuellement utilisée lors du module 3.1 de 3è année à l'Ecole de Médecine à Lausanne. Summary : Since the early days of sexual selection, our understanding of the selective forces acting on males and females during reproduction has increased remarkably. However, despite a long tradition of experimental and theoretical work in this field and relentless effort, numerous questions remain unanswered and many results are conflicting. Moreover, the interface between sexual selection and conservation biology has to date received little attention, despite existing evidence for its importance. In the present thesis, I first used an empirical approach to test various sexual selection hypotheses in a population of whitefish of central Switzerland. This precise population is characterized by a high prevalence of gonadal alterations in males. In particular, I challenged the hypothesis that whitefish males displaying peculiar gonadal features are of lower genetic quality than other seemingly normal males. Additionally, I also worked on identifying important determinant of sperm behavior. During a second theoretical part of my work, which is part of a larger project on the evolution of female mate preferences in harvested fish populations, I developed an individual-based simulation model to estimate how different mate discrimination costs affect the demographical behavior of fish populations and the evolutionary trajectories of female mate preferences. This latter work provided me with some insight on a recently published article addressing the importance of sexual selection for harvesting-induced evolution. I built upon this insight in a short perspective paper. In parallel, I let some methodological questions drive my thoughts, and wrote an essay about possible synergies between the biological, the philosophical and the statistical approach to biological questions.