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1.
Schweiz Arch Tierheilkd ; 165(9): 573-584, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37646097

ABSTRACT

INTRODUCTION: This study aimed to describe equine transportation practices and transport-related behavioural and health problems in Switzerland and to identify possible associations between them. An online survey was disseminated to Swiss equine industry members and questioned respondents' details, transport practices (before, during, and after journeys), horse transport-related behavioural (TRPBs) and health problems (TRHPs) experienced in the previous 2 years. The survey generated 441 valid responses, analysed using descriptive statistics and logistic regression models (outcomes: TRPBs, TRHPs, injuries, diarrhea). Respondents were mainly women (79,5 %), younger than 50 years (75 %), and amateurs (80 %). Most of the respondents transported one or two horses (88,7 %), for a short (< 2 hours) journey (75,5 %). Pre-transport practices were performed by 72,1 % of respondents and horses' fitness for travel was assessed in the majority of cases (66,5 %). During the journey, horses were tethered (92,6 %) and monitored (52,7 %). The majority of respondents (74,9 %) assessed also the horses' fitness after travel. TRPBs were reported by 13,4 % of respondents. TRPBs' likelihood increased when the respondents were women, performed pre-transport practices and training for transport, did not assess drinking behaviour and general health before journey, and the horses experienced also TRHPs. TRHPs were reported by 34 % of the respondents and were associated with younger respondents, use of trucks, doing pre-transport practices, wearing protections, not monitoring horses during transport and preexisting TRPBs. Among TRHPs the most frequent were injuries (72,1 %) and diarrhea (41 %). The likelihood of injuries increased with younger respondents, use of trucks, wearing protections, lack of monitoring during transport and TRPBs. While younger respondents, longer journeys, wearing protections, lack of monitoring during transport, measuring rectal temperature after journeys and TRPBs increased the odds of reporting diarrhea. Even though our findings must be interpreted with caution due to survey limitations, considering that the found associations do not always mean causation, they highlight the strengths and weaknesses of transport practices in Switzerland and report evidence to implement current regulations on the protection of horse welfare during transport.


INTRODUCTION: Cette étude a pour but de décrire les pratiques de transport de chevaux et les problèmes de comportement et de santé liés à ces transports en Suisse et d'identifier les associations possibles entre ces deux éléments. Une enquête en ligne a été diffusée auprès des membres de la filière équine suisse et a permis de recueillir les coordonnées des répondants, les pratiques de transport (avant, pendant et après les trajets), les problèmes de comportement (TRPB) et de santé liés (TRHP) au transport des chevaux rencontrés au cours des deux années précédentes. L'enquête a généré 441 réponses valides, analysées à l'aide de statistiques descriptives et de modèles de régression logistique (résultats: TRPB, TRHP, blessures, diarrhée). Les répondants étaient principalement des femmes (79,5 %), âgées de moins de 50 ans (75 %) et amateurs (80 %). La plupart des personnes interrogées ont transporté un ou deux chevaux (88,7 %), pour un trajet court (< 2 heures) (75,5 %). Des mesures préalables au transport ont été prises par 72,1 % des répondants et l'aptitude des chevaux au voyage a été évaluée dans la majorité des cas (66,5 %). Pendant le voyage, les chevaux étaient attachés (92,6 %) et surveillés (52,7 %). La majorité des répondants (74,9 %) ont également évalué l'état des chevaux après le voyage. Des cas de TRPB ont été signalés par 13,4 % des répondants. La probabilité de TRPB augmente lorsque les personnes interrogées sont des femmes, qu'elles ont pris des mesures préalables au transport et ont entraîné le transport, qu'elles n'ont pas évalué le comportement d'abreuvement et l'état de santé général avant le voyage et que les chevaux ont souffert de TRHP. Les TRHP ont été signalées par 34 % des personnes interrogées et ont été associées à des personnes plus jeunes, à l'utilisation de camions, aux mesures préalables au transport, au port de protections, à l'absence de surveillance des chevaux pendant le transport et à des TRPB préexistantes. Parmi les TRHP, les plus fréquentes étaient les blessures (72,1 %) et la diarrhée (41 %). La probabilité de blessures augmente avec la jeunesse des répondants, l'utilisation de camions, le port de protections, l'absence de surveillance pendant le transport et la présence de TRPB. En revanche, les répondants plus jeunes, les trajets plus longs, le port de protections, l'absence de contrôle pendant le transport, la mesure de la température rectale après les trajets et les TRPB augmentent la probabilité de déclarer une diarrhée. Même si nos résultats doivent être interprétés avec prudence en raison des limites de l'enquête, considérant que les associations trouvées ne signifient pas toujours une causalité, ils soulignent les forces et les faiblesses des pratiques de transport en Suisse et rapportent des preuves pour mettre en œuvre les réglementations actuelles sur la protection du bien-être des chevaux pendant le transport.


Subject(s)
Diarrhea , Transportation , Female , Horses , Animals , Male , Switzerland , Diarrhea/veterinary
2.
Hum Reprod ; 36(9): 2514-2528, 2021 08 18.
Article in English | MEDLINE | ID: mdl-34333622

ABSTRACT

STUDY QUESTION: Does LH protect mouse oocytes and female fertility from alkylating chemotherapy? SUMMARY ANSWER: LH treatment before and during chemotherapy prevents detrimental effects on follicles and reproductive lifespan. WHAT IS KNOWN ALREADY: Chemotherapies can damage the ovary, resulting in premature ovarian failure and reduced fertility in cancer survivors. LH was recently suggested to protect prepubertal mouse follicles from chemotoxic effects of cisplatin treatment. STUDY DESIGN, SIZE, DURATION: This experimental study investigated LH effects on primordial follicles exposed to chemotherapy. Seven-week-old CD-1 female mice were randomly allocated to four experimental groups: Control (n = 13), chemotherapy (ChT, n = 15), ChT+LH-1x (n = 15), and ChT+LH-5x (n = 8). To induce primary ovarian insufficiency (POI), animals in the ChT and ChT+LH groups were intraperitoneally injected with 120 mg/kg of cyclophosphamide and 12 mg/kg of busulfan, while control mice received vehicle. For LH treatment, the ChT+LH-1x and ChT+LH-5x animals received a 1 or 5 IU LH dose, respectively, before chemotherapy, then a second LH injection administered with chemotherapy 24 h later. Then, two animals/group were euthanized at 12 and 24 h to investigate the early ovarian response to LH, while remaining mice were housed for 30 days to evaluate short- and long-term reproductive outcomes. The effects of LH and chemotherapy on growing-stage follicles were analyzed in a parallel experiment. Seven-week-old NOD-SCID female mice were allocated to control (n = 5), ChT (n = 5), and ChT+LH-1x (n = 6) groups. Animals were treated as described above, but maintained for 7 days before reproductive assessment. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the first experiment, follicular damage (phosphorylated H2AX histone (γH2AX) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay), apoptotic biomarkers (western blot), and DNA repair pathways (western blot and RT-qPCR) were assessed in ovaries collected at 12 and 24 h to determine early ovarian responses to LH. Thirty days after treatments, remaining mice were stimulated (10 IU of pregnant mare serum gonadotropin (PMSG) and 10 IU of hCG) and mated to collect ovaries, oocytes, and embryos. Histological analysis was performed on ovarian samples to investigate follicular populations and stromal status, and meiotic spindle and chromosome alignment was measured in oocytes by confocal microscopy. Long-term effects were monitored by assessing pregnancy rate and litter size during six consecutive breeding attempts. In the second experiment, mice were stimulated and mated 7 days after treatments and ovaries, oocytes, and embryos were collected. Follicular numbers, follicular protection (DNA damage and apoptosis by H2AX staining and TUNEL assay, respectively), and ovarian stroma were assessed. Oocyte quality was determined by confocal analysis. MAIN RESULTS AND THE ROLE OF CHANCE: LH treatment was sufficient to preserve ovarian reserve and follicular development, avoid atresia, and restore ovulation and meiotic spindle configuration in mature oocytes exposed at the primordial stage. LH improved the cumulative pregnancy rate and litter size in six consecutive breeding rounds, confirming the potential of LH treatment to preserve fertility. This protective effect appeared to be mediated by an enhanced early DNA repair response, via homologous recombination, and generation of anti-apoptotic signals in the ovary a few hours after injury with chemotherapy. This response ameliorated the chemotherapy-induced increase in DNA-damaged oocytes and apoptotic granulosa cells. LH treatment also protected growing follicles from chemotherapy. LH reversed the chemotherapy-induced depletion of primordial and primary follicular subpopulations, reduced oocyte DNA damage and granulosa cell apoptosis, restored mature oocyte cohort size, and improved meiotic spindle properties. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This was a preliminary study performed with mouse ovarian samples. Therefore, preclinical research with human samples is required for validation. WIDER IMPLICATIONS OF THE FINDINGS: The current study tested if LH could protect the adult mouse ovarian reserve and reproductive lifespan from alkylating chemotherapy. These findings highlight the therapeutic potential of LH as a complementary non-surgical strategy for preserving fertility in female cancer patients. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Regional Valencian Ministry of Education (PROMETEO/2018/137), the Spanish Ministry of Science and Innovation (CP19/00141), and the Spanish Ministry of Education, Culture and Sports (FPU16/05264). The authors declare no conflict of interest.


Subject(s)
Ovarian Reserve , Alkylating Agents/toxicity , Animals , Female , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Ovarian Follicle , Pregnancy
3.
J Eur Acad Dermatol Venereol ; 34(4): 691-708, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31541557

ABSTRACT

BACKGROUND: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. OBJECTIVES: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. METHODS: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. RESULTS: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2  = 0%), while a significant heterogeneity (I2  > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. CONCLUSIONS: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.


Subject(s)
Melanoma/chemically induced , Occupational Diseases/chemically induced , Occupational Exposure/adverse effects , Pesticides/toxicity , Skin Neoplasms/chemically induced , Humans , Melanoma, Cutaneous Malignant
4.
Hum Reprod Update ; 25(6): 673-693, 2019 11 05.
Article in English | MEDLINE | ID: mdl-31600388

ABSTRACT

BACKGROUND: Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to the effects of chemotherapy and radiotherapy. While oocyte, embryo and ovarian cortex cryopreservation can help some women with cancer-induced infertility achieve pregnancy, the development of effective methods to protect ovarian function during chemotherapy would be a significant advantage. OBJECTIVE AND RATIONALE: This paper critically discusses the different damaging effects of the most common chemotherapeutic compounds on the ovary, in particular, the ovarian follicles and the molecular pathways that lead to that damage. The mechanisms through which fertility-protective agents might prevent chemotherapy drug-induced follicle loss are then reviewed. SEARCH METHODS: Articles published in English were searched on PubMed up to March 2019 using the following terms: ovary, fertility preservation, chemotherapy, follicle death, adjuvant therapy, cyclophosphamide, cisplatin, doxorubicin. Inclusion and exclusion criteria were applied to the analysis of the protective agents. OUTCOMES: Recent studies reveal how chemotherapeutic drugs can affect the different cellular components of the ovary, causing rapid depletion of the ovarian follicular reserve. The three most commonly used drugs, cyclophosphamide, cisplatin and doxorubicin, cause premature ovarian insufficiency by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. They also cause an increase in damage to blood vessels and the stromal compartment and increment inflammation. In the past 20 years, many compounds have been investigated as potential protective agents to counteract these adverse effects. The interactions of recently described fertility-protective agents with these damage pathways are discussed. WIDER IMPLICATIONS: Understanding the mechanisms underlying the action of chemotherapy compounds on the various components of the ovary is essential for the development of efficient and targeted pharmacological therapies that could protect and prolong female fertility. While there are increasing preclinical investigations of potential fertility preserving adjuvants, there remains a lack of approaches that are being developed and tested clinically.


Subject(s)
Antineoplastic Agents/adverse effects , Fertility Preservation/methods , Infertility, Female/chemically induced , Ovarian Follicle/pathology , Ovarian Reserve/drug effects , Primary Ovarian Insufficiency/chemically induced , Cisplatin/adverse effects , Cryopreservation , Cyclophosphamide/adverse effects , Doxorubicin/adverse effects , Female , Fertility/physiology , Humans , Oocytes/physiology , Pregnancy
5.
J Geophys Res Space Phys ; 121(1): 338-357, 2016 01.
Article in English | MEDLINE | ID: mdl-27610291

ABSTRACT

Studies of Saturn's magnetosphere with the Cassini mission have established the importance of Enceladus as the dominant mass source for Saturn's magnetosphere. It is well known that the ionosphere is an important mass source at Earth during periods of intense geomagnetic activity, but lesser attention has been dedicated to study the ionospheric mass source at Saturn. In this paper we describe a case study of data from Saturn's magnetotail, when Cassini was located at ≃ 2200 h Saturn local time at 36 RS from Saturn. During several entries into the magnetotail lobe, tailward flowing cold electrons and a cold ion beam were observed directly adjacent to the plasma sheet and extending deeper into the lobe. The electrons and ions appear to be dispersed, dropping to lower energies with time. The composition of both the plasma sheet and lobe ions show very low fluxes (sometimes zero within measurement error) of water group ions. The magnetic field has a swept-forward configuration which is atypical for this region, and the total magnetic field strength is larger than expected at this distance from the planet. Ultraviolet auroral observations show a dawn brightening, and upstream heliospheric models suggest that the magnetosphere is being compressed by a region of high solar wind ram pressure. We interpret this event as the observation of ionospheric outflow in Saturn's magnetotail. We estimate a number flux between (2.95 ± 0.43) × 109 and (1.43 ± 0.21) × 1010 cm-2 s-1, 1 or about 2 orders of magnitude larger than suggested by steady state MHD models, with a mass source between 1.4 ×102 and 1.1 ×103 kg/s. After considering several configurations for the active atmospheric regions, we consider as most probable the main auroral oval, with associated mass source between 49.7 ±13.4 and 239.8 ±64.8 kg/s for an average auroral oval, and 10 ±4 and 49 ±23 kg/s for the specific auroral oval morphology found during this event. It is not clear how much of this mass is trapped within the magnetosphere and how much is lost to the solar wind.

6.
Cell Death Dis ; 6: e1906, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26469955

ABSTRACT

Stem cells are unique cell types capable to proliferate, some of them indefinitely, while maintaining the ability to differentiate into a few or any cell lineages. In 2003, a group headed by Hans R. Schöler reported that oocyte-like cells could be produced from mouse embryonic stem (ES) cells in vitro. After more than 10 years, where have these researches reached? Which are the major successes achieved and the problems still remaining to be solved? Although during the last years, many reviews have been published about these topics, in the present work, we will focus on an aspect that has been little considered so far, namely a strict comparison between the in vitro and in vivo developmental capabilities of the primordial germ cells (PGCs) isolated from the embryo and the PGC-like cells (PGC-LCs) produced in vitro from different types of stem cells in the mouse, the species in which most investigation has been carried out. Actually, the formation and differentiation of PGCs are crucial for both male and female gametogenesis, and the faithful production of PGCs in vitro represents the basis for obtaining functional germ cells.


Subject(s)
Gametogenesis , Germ Cells/physiology , Stem Cells/physiology , Animals , Cell Differentiation , Cells, Cultured , Humans
7.
Cell Cycle ; 14(7): 1036-45, 2015.
Article in English | MEDLINE | ID: mdl-25603532

ABSTRACT

As the name implies, Stimulated by Retinoic Acid 8 is an early retinoic acid (RA) responsive gene pivotal for the beginning of meiosis in female and male germ cells. Its expression is strictly time-dependent and cell-specific (pre-meiotic germ cells) and likely requires a complex mechanism of regulation. In this study, we demonstrate a direct negative control of SOHLH1 and SOHLH2, 2 germ cell specific bHLH transcription factors, on Stra8 expression. We observed a negative correlation between STRA8 and SOHLH1 expression in prepuberal differentiating mouse KIT(+) spermatogonia and found that SOHLH1 and SOHLH2 were able to directly and cooperatively repress STRA8 expression in cell lines in vitro through binding to its promoter. We also identified 2 canonical E-Box motives in the Stra8 promoter that mediated the negative regulation of SOHLH1 and SOHLH2 on these gene both in the cell lines and KIT(+) spermatogonia. We hypothesize that this novel negative activity of SOHLH1 and SOHLH2 in male cooperates with that of other transcription factors to coordinate spermatogonia differentiation and the RA-induced meiosis and in female ensures STRA8 down-regulation at mid-end stages of meiotic prophase I.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Basic Helix-Loop-Helix Transcription Factors/physiology , Adaptor Proteins, Signal Transducing/genetics , Base Sequence , Cell Differentiation , Down-Regulation , Gene Expression , Gene Silencing , HEK293 Cells , Humans , Male , Molecular Sequence Data , Promoter Regions, Genetic , Protein Binding , Spermatogonia/physiology
8.
Andrology ; 3(2): 265-70, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25598385

ABSTRACT

Measurement of reactive oxygen species (ROS) producing leukocytes in semen has been a standard component of the semen analysis, but its true significance remains still unknown. In this study, we have correlated the number of seminal leukocytes to various semen parameters. We found a negative correlation between the leukocyte number and sperm concentration (rs  = -0.22; p = 0.01) and motility (rs  = -0.20; p = 0.02). In contrast, a positive correlation between the number of leukocytes and both seminal ROS (rs  = 0.70, p < 0.001; n = 125) and the number of spermatozoa with DNA fragmentation (rs  = 0.43, p = 0.032; n = 25) was found. However, only a trend of positive correlation between ROS and the number of spermatozoa with TUNEL-detected DNA fragmentation was observed. Moreover, this latter was not correlated with loss of sperm mitochondrial membrane potential (MMP) (10% vs 35%, rs  = 0.25, p = 0.08; n = 50). Overall these results indicate that the presence of high number of leukocytes in the ejaculate negatively affects key semen parameters, as sperm concentration and motility, associated with infertility conditions. Moreover, they suggest that leukocytes are the major source of the seminal ROS and cause of sperm DNA fragmentation. However, the absence of a clear correlation between ROS and sperm DNA fragmentation, and spermatozoa with damaged DNA and MMP loss, suggest that ROS produced by leukocytes might be not the only cause of DNA damage in spermatozoa and that intrinsic mitochondrial-dependent apoptotic pathways might not have a major impact on sperm DNA fragmentation.


Subject(s)
DNA Damage , Leukocytes/cytology , Membrane Potential, Mitochondrial , Reactive Oxygen Species/metabolism , Semen/cytology , Spermatozoa/cytology , Humans , Male
9.
J Geophys Res Space Phys ; 120(5): 3603-3617, 2015 05.
Article in English | MEDLINE | ID: mdl-27570722

ABSTRACT

We present a case study of an event from 20 August (day 232) of 2006, when the Cassini spacecraft was sampling the region near 32 RS and 22 h LT in Saturn's magnetotail. Cassini observed a strong northward-to-southward turning of the magnetic field, which is interpreted as the signature of dipolarization of the field as seen by the spacecraft planetward of the reconnection X line. This event was accompanied by very rapid (up to ~1500 km s-1) thermal plasma flow toward the planet. At energies above 28 keV, energetic hydrogen and oxygen ion flow bursts were observed to stream planetward from a reconnection site downtail of the spacecraft. Meanwhile, a strong field-aligned beam of energetic hydrogen was also observed to stream tailward, likely from an ionospheric source. Saturn kilometric radiation emissions were stimulated shortly after the observation of the dipolarization. We discuss the field, plasma, energetic particle, and radio observations in the context of the impact this reconnection event had on global magnetospheric dynamics.

10.
Nanotechnology ; 22(46): 465203, 2011 Nov 18.
Article in English | MEDLINE | ID: mdl-22032901

ABSTRACT

The coupling of a prescribed number of site-controlled pyramidal quantum dots (QDs) with photonic crystal (PhC) cavities was studied by polarization and power-dependent photoluminescence measurements. The energy of the cavity mode could be readily tuned, making use of the high spectral uniformity of the QDs and designing PhC cavities with different hole radii. Efficient coupling of the PhC cavity modes both to the ground state and to the excited state transitions of the QDs was observed, whereas no evidence for far off-resonant coupling was found.

11.
Phys Rev Lett ; 106(22): 227402, 2011 Jun 03.
Article in English | MEDLINE | ID: mdl-21702633

ABSTRACT

We demonstrate that the emission characteristics of site-controlled InGaAs/GaAs single quantum dots embedded in photonic crystal slab cavities correspond to single confined excitons coupled to cavity modes, unlike previous reports of similar systems based on self-assembled quantum dots. By using polarization-resolved photoluminescence spectroscopy at different temperatures and a theoretical model, we show that the exciton-cavity interaction range is limited to the phonon sidebands. Photon-correlation and pump-power dependence experiments under nonresonant excitation conditions further establish that the cavity is fed only by a single exciton.

12.
Nanotechnology ; 20(41): 415205, 2009 Oct 14.
Article in English | MEDLINE | ID: mdl-19762950

ABSTRACT

Arrays of site-controlled, pyramidal InGaAs/GaAs quantum dots (QDs) grown by organo-metallic chemical vapour deposition with densities comparable to those of self-assembled QDs (5 x 10(9) cm(-2)) are demonstrated. The QDs exhibit high quality photoluminescence spectra with inhomogeneous broadening of only 6.5 meV. The QD dipole moment was estimated through the analysis of time-resolved photoluminescence measurements. Such ordered QD arrays should be useful for applications in active nanophotonic systems such as QD lasers, modulators and switches requiring high overlap of the optical modes with the QD active region.


Subject(s)
Luminescent Measurements/methods , Nanotechnology/methods , Quantum Dots , Temperature
13.
Ann N Y Acad Sci ; 1163: 475-7, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19456391

ABSTRACT

Here we show that genistein, through an estrogen receptor-mediated action, modulates gene expression in the mouse testis throughout development. Genistein passed from the lactating mother to the suckling offspring at levels sufficient to activate gene expression in the testis of the pups. Testis are already responsive to genistein as well as to estradiol at day 14.5 of fetal development. Activation of luciferase correlates with an activation of cell proliferation. In conclusion, our results show that genistein affects reproductive organs of male mice at all developmental ages.


Subject(s)
Genistein/pharmacology , Receptors, Estrogen/metabolism , Testis/drug effects , Testis/metabolism , Transcriptional Activation/drug effects , Transcriptional Activation/genetics , Animals , Male , Mice , Mice, Transgenic , Receptors, Estrogen/genetics , Tissue Culture Techniques
14.
Phys Med Biol ; 53(20): 5675-88, 2008 Oct 21.
Article in English | MEDLINE | ID: mdl-18812651

ABSTRACT

Myelin is a multi-lamellar membrane surrounding neuronal axons and increasing their conduction velocity. When investigated by small-angle x-ray scattering (SAXS), the lamellar quasi-periodical arrangement of the myelin sheath gives rise to distinct peaks, which allow the determination of its molecular organization and the dimensions of its substructures. In this study we report on the myelin sheath structural determination carried out on a set of human brain tissue samples coming from surgical biopsies of two patients: a man around 60 and a woman nearly 90 years old. The samples were extracted either from white or grey cerebral matter and did not undergo any manipulation or chemical-physical treatment, which could possibly have altered their structure, except dipping them into a formalin solution for their conservation. Analysis of the scattered intensity from white matter of intact human cerebral tissue allowed the evaluation not only of the myelin sheath periodicity but also of its electronic charge density profile. In particular, the thicknesses of the cytoplasm and extracellular regions were established, as well as those of the hydrophilic polar heads and hydrophobic tails of the lipid bilayer. SAXS patterns were measured at several locations on each sample in order to establish the statistical variations of the structural parameters within a single sample and among different samples. This work demonstrates that a detailed structural analysis of the myelin sheath can also be carried out in randomly oriented samples of intact human white matter, which is of importance for studying the aetiology and evolution of the central nervous system pathologies inducing myelin degeneration.


Subject(s)
Brain/diagnostic imaging , Brain/ultrastructure , Myelin Sheath/diagnostic imaging , Myelin Sheath/ultrastructure , Scattering, Small Angle , X-Ray Diffraction/methods , Humans , Molecular Conformation , Radiography
15.
Reproduction ; 134(2): 241-52, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17660234

ABSTRACT

We report a short-term culture system that allows to define novel characteristic of programmed cell death (PCD) in fetal oocytes and to underscore new aspects of this process. Mouse fetal oocytes cultured in conditions allowing meiotic prophase I progression underwent apoptotic degeneration waves as revealed by TUNEL staining. TEM observations revealed recurrent atypical apoptotic morphologies characterized by the absence of chromatin margination and nuclear fragmentation; oocytes with autophagic and necrotic features were also observed. Further characterization of oocyte death evidenced DNA ladder, Annexin V binding, PARP cleavage, and usually caspase activation (namely caspase-2). In the aim to modulate the oocyte death process, we found that the addition to the culture medium of the pan-caspase inhibitors Z-VAD or caspase-2-specific inhibitor Z-VDVAD resulted in a partial and transient prevention of this process. Oocyte death was significantly reduced by the antioxidant agent NAC and partly prevented by KL and IGF-I growth factors. Finally, oocyte apoptosis was reduced by calpain inhibitor I and increased by rapamycin after prolonged culture. These results support the notion that fetal oocytes undergo degeneration mostly by apoptosis. This process is, however, often morphologically atypical and encompasses other forms of cell death including caspase-independent apoptosis and autophagia. The observation that oocyte death occurs mainly at certain stages of meiosis and can only be attenuated by typical anti-apoptotic treatments favors the notion that it is controlled at least in part by stage-specific oocyte-autonomous meiotic checkpoints and when activated is little amenable to inhibition being the oocyte able to switch back and forth among different death pathways.


Subject(s)
Apoptosis/physiology , Fetus/physiology , Meiotic Prophase I/physiology , Oocytes/cytology , Ovary/cytology , Acetylcysteine/pharmacology , Animals , Antioxidants/pharmacology , Apoptosis/drug effects , Autophagy , Caspase Inhibitors , Cell Culture Techniques , Cells, Cultured , Cysteine Proteinase Inhibitors/pharmacology , DNA Fragmentation , Female , Glycoproteins/pharmacology , Immunosuppressive Agents/pharmacology , In Situ Nick-End Labeling , Insulin-Like Growth Factor I/pharmacology , Mice , Mice, Inbred Strains , Microscopy, Electron, Transmission , Necrosis , Oligopeptides/pharmacology , Oocytes/drug effects , Oocytes/ultrastructure , Sirolimus/pharmacology , Stem Cell Factor/pharmacology
16.
Phys Rev Lett ; 98(14): 146402, 2007 Apr 06.
Article in English | MEDLINE | ID: mdl-17501294

ABSTRACT

The dependence of the electron mass on hydrostatic pressure P in N-diluted GaAs1-xNx (x=0.10% and 0.21%) is investigated by magnetophotoluminescence. Exceedingly large fluctuations (up to 60%/kbar) in the electron mass with increasing P are found. These originate from a pressure-driven tuning of the hybridization degree between the conduction band minimum and specific nitrogen-related states. Present results suggest a hierarchy between different nitrogen complexes as regards the extent of the perturbation these complexes exert on the electronic properties of the GaAs host.

17.
Hum Reprod ; 21(12): 3185-92, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16905672

ABSTRACT

BACKGROUND: There is much evidence involving the KIT tyrosine kinase receptor and its ligand KITLG in the survival and proliferation of germ cells. Animal models and functional studies in humans suggest that this signalling pathway plays a role in male infertility. METHODS: We studied three and two single-nucleotide polymorphisms (SNPs) (rs3819392, rs3134885, rs2237012, rs10506957 and rs995030) located within the genomic region of the KIT and KITLG genes, respectively. A total of 167 idiopathic infertile men (sperm counts <5 million spz/ml) and 465 unrelated healthy controls from the same geographical region were genotyped for these SNPs. RESULTS: We found a statistically significant association of the rs3819392 polymorphism, which is located within the KIT gene, with idiopathic male infertility. In addition, a deviation from the Hardy-Weinberg equilibrium (HWE) law was observed for rs10506957 polymorphism within the KITLG gene only in the infertile group. CONCLUSIONS: Our data indicate that the KIT/KITLG system may be involved in a low sperm count trait in humans.


Subject(s)
Genetic Markers/genetics , Infertility, Male/genetics , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins c-kit/genetics , Stem Cell Factor/genetics , Chromosome Mapping , Gene Frequency , Haplotypes , Humans , Infertility, Male/etiology , Male
18.
Med Phys ; 32(8): 2455-63, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16193774

ABSTRACT

We present EGS4 Monte Carlo calculations of the spatial distribution of the dose deposited by a single x-ray pencil beam, a planar microbeam, and an array of parallel planar microbeams as used in radiation therapy research. The profiles of the absorbed dose distribution in a phantom, including the peak-to-valley ratio of the dose distribution from microbeam arrays, were calculated at micrometer resolution. We determined the dependence of the findings on the main parameters of photon and electron transport. The results illustrate the dependence of the electron range and the deposited in-beam dose on the cut-off energy, of the electron transport, as well as the effects on the dose profiles of the beam energy, the array size, and the beam spacing. The effect of beam polarization also was studied for a single pencil beam and for an array of parallel planar microbeams. The results show that although the polarization effect on the dose distribution from a 3 cm x 3 cm microbeam array inside a water phantom is large enough to be measured at the outer side of the array (16% difference of the deposited dose for x-ray beams of 200 keV), it is not detectable at the array's center, thus being irrelevant for the radiation therapy purposes. Finally we show that to properly compare the dose profiles determined with a metal oxide semiconductor field emission transistor detector with the computational method predictions, it is important to simulate adequately the size and the material of the device's Si active element.


Subject(s)
Models, Biological , Radiometry/methods , Radiotherapy Planning, Computer-Assisted/methods , Software , Body Burden , Computer Simulation , Models, Statistical , Monte Carlo Method , Radiotherapy Dosage , Relative Biological Effectiveness , Scattering, Radiation , X-Ray Therapy/methods , X-Rays
19.
Phys Rev Lett ; 94(5): 050602, 2005 Feb 11.
Article in English | MEDLINE | ID: mdl-15783623

ABSTRACT

An exact "branch by branch" calculation of the diffusional flux is proposed for partially absorbed random walks on arbitrary tree structures. In the particular case of symmetric trees, an explicit analytical expression is found which is valid whatever the size of the tree. Its application to the respiratory phenomena in pulmonary acini gives an analytical description of the crossover regime governing the human lung efficiency.


Subject(s)
Models, Biological , Oxygen/chemistry , Oxygen/metabolism , Pulmonary Alveoli/chemistry , Pulmonary Alveoli/metabolism , Pulmonary Gas Exchange/physiology , Animals , Computer Simulation , Diffusion , Humans , Models, Statistical
20.
Respir Physiol Neurobiol ; 145(2-3): 279-93, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15705542

ABSTRACT

Gas exchange at the acinar level involves several physico-chemical phenomena within a complex geometry. A gas transport model, which takes into account both the diffusion into the acinus and the diffusion across the alveolar membrane, is used to understand gas mixing in realistic systems. It is first shown that the behaviour of the system, computed on model geometries in 3D, only depends on the topological structure of the acinus. Taking advantage of this property, a new efficient method based on random walks on a lattice is used to compute gas diffusion in structures taken from real morphological data. This approach shows that, at rest, the human acinus efficiency is only 30-40%. These results provide a new evidence of the existence of diffusional screening at the acinar level. This implies permanent spatial inhomogeneity of oxygen and carbon dioxide partial pressure. The notion of an "alveolar gas" is reinterpreted as a spatial average of the gas distribution. This model casts new light on the respiratory properties of other gas mixtures, such as helium-oxygen.


Subject(s)
Models, Biological , Pulmonary Alveoli/physiology , Pulmonary Gas Exchange , Cell Membrane Permeability/physiology , Diffusion , Humans , Oxygen Consumption/physiology , Partial Pressure , Pulmonary Alveoli/anatomy & histology
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