"Judicial Activism in the ""Eye of the Beholder"" : the Israeli High Court of Justice and the Human Rights of the Palestinians in the Occupied Territories"

Il est mondialement reconnu que les institutions judiciaires jouent un rôle central dans le processus de prise de décisions politiques, à la fois au niveau national et international. C’est d’ailleurs le cas à la Haute Cour de justice d’Israël. L’étendue de son succès (ou de son échec) dans la tentative de trouver une solution aux violations des droits humains dans les territoires occupés est un problème qui continue de faire l’objet de bien des débats et de recherches académiques. À cet égard, il a été suggéré que, malgré l’absence de constitution écrite et l’existence d’un état d’urgence prolongé en Israël, la Haute Cour de justice a réussi à adopter une approche « judiciairement active » quant à la protection et la promotion des droits de l’homme de manière générale, y compris ceux des Palestiniens dans les territoires occupés. Dans cette perspective, le débat sur le processus d’examen judiciaire de la Haute Cour de Justice tient pour acquise la notion qu’Israël est une démocratie. Ainsi, cet article cherche à examiner cette hypothèse. Premièrement, en adoptant la position que le processus de révision judiciaire est compatible avec la démocratie et la règle de loi. Deuxièmement, il examine l’approche « judiciairement active » de la Cour et soumet un bref aperçu du processus, des outils et des principes légaux que la Cour adopte pour examiner les actions des autorités israéliennes, y compris l’armée, et imposer une loi commune de protection des droits de la personne, donc ceux des Palestiniens dans les territoires occupés. L’article argumente également que le contrôle prolongé des territoires occupés par Israël a eu des conséquences significatives, car tout effort fourni par la Cour pour garantir le respect des droits humains de la population civile palestinienne doit se faire sans compromettre la sécurité du pouvoir israélien. La conclusion à laquelle on arrive ici dépend de la façon dont on qualifie ce contrôle: une occupation à long terme ou une annexion (ce qui n’est pas réglementaire par rapport à loi internationale), ce qui n’est pas sans conséquence sur le rôle que la Haute Cour de justice peut effectivement jouer pour faire respecter les droits de la personne dans les territoires occupés.

The Assault on Human Rigths and the Resilience of the Andean Dream: Health Inequities in Ecuador. IV Annual Distinguished Lecture sponsored by the Center for Research on Ethnicity, Culture and Health; School of Public Health; University of Michigan

The point of departure for these reflections is life, since its protection is the central purpose encouraging the defense of human rights and of public health. Life in the Andes has an exceptional diversity. Particularly in Ecuador, my country, this diversity constitutes a characteristic sign that is expressed in two main forms: natural megadiversity and multiculturalism. Indeed, Ecuador’s small territory synthesizes practically all types of lifezones that exist on Earth, having received the gift of high average rates of solar energy and abundant nutritional sources, which have facilitated the natural reproduction of countless species that show their beautiful vitality in the variety of ecosystems that compose the Andean mountain range, the tropical plains, the Amazon humid forests, and the Galapagos Islands. But besides being a highly biodiverse country, it is also a plurinational and multi-cultural society, in which the activity of human beings, organized into social conglomerates of different historical and cultural backgrounds, have formed more than a dozen nations and peoples. Regrettably this natural and human wealth has not been able to bear its best fruits due to the violent operation of a deep social inequity – unfortunately also one of the highest in the Americas—which conspires against life and is reproduced in national and international inequitable relations. This structural inequity has changed its form throughout the centuries and currently has reached its highest and most perverse level of development.

From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway.

Human-animal interaction, stress, and embryo production in Bos indicus embryo donors under tropical conditions

This study investigated the effect of human-animal interaction (HAI) and the stress response on the quality of embryo production in superovulated Nelore (Bos indicus) cattle, under tropical conditions. Thirty-two females underwent a superovulation protocol for 5 days. Cortisol concentrations were determined in blood plasma collected on days 0, 4, and 5. Artificial insemination was performed on days 4 and 5, and nonsurgical embryo flushing on day 11. Embryo production and viability were determined. Human stimulation, animal behaviors, accidents, and handling time were recorded to assess HAI. Cattle age was negatively correlated with accidents, frequency of aversive behaviors, and negative stimuli by stockperson during transit through corral compartments to receive superovulation treatments. The factor analysis revealed two distinct groups. The first group was called stressed and had higher cortisol concentration than the nonstressed group, 16.0 +/- 2.1 and 12.5 +/- 1.0 ng/mL, respectively. Comparisons between these groups showed that the frequency of voice emissions by the stockperson and the number of accidents were higher in the stressed group, and also, the mean handling time was longer in the stressed group than for the nonstressed. As a result, viability rate of the embryos was 19% lower in the stressed group (P < 0.05). This indicates that intensive negative HAI is likely related to stress, which affects embryo production in a superovulation program.

Seasonal variability in the fertilization rate of women undergoing assisted reproduction treatments

The objective of this study was to evaluate whether seasonality affects human-assisted reproduction treatment outcomes. For this, 1932 patients undergoing intracytoplasmic sperm injection (ICSI) were assigned to a season group according to the day of oocyte retrieval: winter (n = 435), spring (n = 444), summer (n = 469) or autumn (n = 584). Analysis of variance was used to compare the ICSI outcomes. The fertilization rate was increased during the spring (winter: 67.9%, spring: 73.5%, summer: 68.7% and autumn: 69.0%; p < 0.01). In fact, a nearly 50% increase in the fertilization rate during the spring was observed (odds ratio 1.45, confidence interval 1.20-1.75; p < 0.01). The oestradiol concentration per number of oocytes was significantly higher during the spring (winter: 235.8 pg/mL, spring: 282.1 pg/mL, summer: 226.1 pg/mL and autumn: 228.7 pg/mL; p = 0.030). This study demonstrates a seasonal variability in fertilization after ICSI, where fertilization is higher during the spring than at any other time.

GnRH agonist versus GnRH antagonist in assisted reproduction cycles: oocyte morphology

Background: The selection of developmentally competent human gametes may increase the efficiency of assisted reproduction. Spermatozoa and oocytes are usually assessed according to morphological criteria. Oocyte morphology can be affected by the age, genetic characteristics, and factors related to controlled ovarian stimulation. However, there is a lack of evidence in the literature concerning the effect of gonadotropin-releasing hormone (GnRH) analogues, either agonists or antagonists, on oocyte morphology. The aim of this randomized study was to investigate whether the prevalence of oocyte dysmorphism is influenced by the type of pituitary suppression used in ovarian stimulation.Methods: A total of 64 patients in the first intracytoplasmic sperm injection (ICSI) cycle were prospectively randomized to receive treatment with either a GnRH agonist with a long-term protocol (n: 32) or a GnRH antagonist with a multi-dose protocol (n: 32). Before being subjected to ICSI, the oocytes at metaphase II from both groups were morphologically analyzed under an inverted light microscope at 400x magnification. The oocytes were classified as follows: normal or with cytoplasmic dysmorphism, extracytoplasmic dysmorphism, or both. The number of dysmorphic oocytes per total number of oocytes was analyzed.Results: Out of a total of 681 oocytes, 189 (27.8 %) were morphologically normal, 220 (32.3 %) showed cytoplasmic dysmorphism, 124 (18.2%) showed extracytoplasmic alterations, and 148 (21.7%) exhibited both types of dysmorphism. No significant difference in oocyte dysmorphism was observed between the agonist- and antagonist- treated groups (P > 0.05). Analysis for each dysmorphism revealed that the most common conditions were alterations in polar body shape (31.3%) and the presence of diffuse cytoplasmic granulations (22.8%), refractile bodies (18.5%) and central cytoplasmic granulations (13.6%). There was no significant difference among individual oocyte dysmorphisms in the agonist- and antagonist-treated groups (P > 0.05).Conclusions: Our randomized data indicate that in terms of the quality of oocyte morphology, there is no difference between the antagonist multi-dose protocol and the long-term agonist protocol. If a GnRH analogue used for pituitary suppression in IVF cycles influences the prevalence of oocyte dysmorphisms, there does not appear to be a difference between the use of an agonist as opposed to an antagonist.

Long-term effects of perinatal androgenization on reproductive parameters of male rat offspring androgenization and male rat reproduction

It is known that during sex differentiation, fetal androgens are critical determinants of the male phenotype. Although testosterone is necessary for normal development of male sexual behavior, perinatal androgen treatment can result in disruption of normal male sexual reproduction. Pregnant Wistar rats were administered either corn oil (vehicle) or testosterone propionate at 0.2 mg/kg from gestational day 12 until the end of lactation and the reproductive function of male offspring was evaluated at 90 (adulthood) and 270 (middle age) days of age. Perinatal androgenization in the rat provoked a reduction in sperm production and reserves in adulthood that did not affect fertility and did not persist at more advanced ages, as shown by the results at post-natal day 270. If perinatal androgenization promotes similar effects in humans of reproductive age, the results of the present work can impact male reproduction health, given the less efficient spermatogenesis and lower sperm reserves in the human epididymis, compared to rodents. © Georg Thieme Verlag KG Stuttgart. New York.

BILL E. KUNKLE INTERDISCIPLINARY BEEF SYMPOSIUM: Temperament and acclimation to human handling influence growth, health, and reproductive responses in Bos taurus and Bos indicus cattle

Temperament in cattle is defined as the fear-related behavioral responses when exposed to human handling. Our group evaluates cattle temperament using 1) chute score on a 1 to 5 scale that increases according to excitable behavior during restraint in a squeeze chute, 2) exit velocity (speed of an animal exiting the squeeze chute), 3) exit score (dividing cattle according to exit velocity into quintiles using a 1 to 5 scale where 1 = cattle in the slowest quintile and 5 = cattle in the fastest quintile), and 4) temperament score (average of chute and exit scores). Subsequently, cattle are assigned a temperament type of adequate temperament (ADQ; temperament score <= 3) or excitable temperament (EXC; temperament score > 3). To assess the impacts of temperament on various beef production systems, our group associated these evaluation criteria with productive, reproductive, and health characteristics of Bos taurus and Bos indicus-influenced cattle. As expected, EXC cattle had greater plasma cortisol vs. ADQ cattle during handling, independent of breed type (B. indicus x B. taurus, P < 0.01; B. taurus, P < 0.01; B. indicus, P = 0.04) or age (cows, P < 0.01; heifers or steers, P < 0.01). In regards to reproduction, EXC females had reduced annual pregnancy rates vs. ADQ cohorts across breed types (B. taurus, P = 0.03; B. indicus, P = 0.05). Moreover, B. taurus EXC cows also had decreased calving rate (P = 0.04), weaning rate (P = 0.09), and kilograms of calf weaned/cow exposed to breeding (P = 0.08) vs. ADQ cohorts. In regards to feedlot cattle, B. indicus EXC steers had reduced ADG (P = 0.02) and G:F (P = 0.03) during a 109-d finishing period compared with ADQ cohorts. Bos taurus EXC cattle had reduced weaning BW (P = 0.04), greater acute-phase protein response on feedlot entry (P <= 0.05), impaired feedlot receiving ADG (P = 0.05), and reduced carcass weight (P = 0.07) vs. ADQ cohorts. Acclimating B. indicus x B. taurus or B. taurus heifers to human handling improved temperament (P <= 0.02), reduced plasma cortisol (P < 0.01), and hastened puberty attainment (P <= 0.02). However, no benefits were observed when mature cows or feeder cattle were acclimated to human handling. In conclusion, temperament impacts productive, reproductive, and health characteristics of beef cattle independent of breed type. Hence, strategies to improve herd temperament are imperative for optimal production efficiency of beef operations based on B. taurus and B. indicus-influenced cattle.

Impact of the medicine Hydroxyurea on reproduction and development, using Drosophila melanogaster as a model organism

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Induced reproduction and early development histology of Oscar Astronotus ocellatus (Agassiz, 1831)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Inactivating Mutations of the Human Luteinizing Hormone Receptor in Both Sexes

The human luteinizing hormone/chorionic gonadotropin receptor (LHCGR) plays a fundamental role in male and female reproductive physiology. Over the past 15 years, several homozygous or compound heterozygous loss-of-function mutations in the LHCGR gene have been described in males and females. In genetic males, mutations in LHCGR were associated with distinct degrees of impairment in pre- and postnatal testosterone secretion resulting in a phenotypic spectrum. Patients with the severe form of LH resistance have predominantly female external genitalia and absence of secondary sex differentiation at puberty. Patients with milder forms have predominantly male external genitalia with micropenis and/or hypospadias or only infertility without ambiguity. The undermasculization is associated with low basal, as well as human CG-stimulated, testosterone levels and elevated LH levels after pubertal age, without abnormal step-up in testosterone biosynthesis precursors. The testes have only slightly reduced size but mature Leydig cells are absent or scarce (Leydig cell hypoplasia). Genetic females with inactivating LHCGR mutations have female external genitalia, spontaneous breast and pubic hair development at puberty, and normal or late menarche followed by oligoamenorrhea and infertility. Estradiol and progesterone levels are normal for the early to midfollicular phase, but do not reach ovulatory or luteal phase levels. Serum LH levels are high whereas follicle-stimulating hormone levels are normal or only slightly increased. Pelvic ultrasound has demonstrated a small or normal uterus and normal or enlarged ovaries with cysts. The inactivating mutations of the LHCGR have provided important insights into distinct physiological roles of LH in reproduction of both sexes.

The use of parthenotegenetic and IVF bovine blastocysts as a model for the creation of human embryonic stem cells under defined conditions

Clinical application of human embryonic stem cells will be possible, when cell lines are created under xeno-free and defined conditions. We aimed to establish methodologies for parthenogenetic activation, culture to blastocyst and mechanical isolation of the inner cell mass (ICM) using bovine oocytes, as a model for derivation and proliferation of human embryonic stem cells under defined xeno-free culture conditions. Cumulus-oocyte-complexes were in vitro matured and activated using Ca(2+)Ionophore and 6-DMAP or in vitro fertilized (IVF). Parthenotes and biparental embryos were cultured to blastocysts, when their ICM was mechanically isolated and placed onto a substrate of fibronectin in StemProA (R) medium. After attachment, primary colonies were left to proliferate and stained for pluripotency markers, alkaline phosphatase and Oct-4. Parthenogenesis and fertilization presented significantly different success rates (91 and 79 %, respectively) and blastocyst formation (40 and 43 %, respectively). ICMs from parthenogenetic and IVF embryos formed primary and expanded colonies at similar rates (39 % and 33 %, respectively). Six out of eight parthenogenetic colonies tested positive for alkaline phosphatase. Three colonies were analyzed for Oct-4 and they all tested positive for this pluripotency marker. Our data show that Ca2+ Ionophore, and 6-DMAP are efficient in creating large numbers of blastocysts to be employed as a model for human oocyte activation and embryo development. After mechanical isolation, parthenogetic derived ICMs showed a good rate of derivation in fibronectin and Stem-Pro forming primary and expanded colonies of putative embryonic stem cells. This methodology may be a good strategy for parthenogenetic activation of discarded human oocytes and derivation in defined conditions for future therapeutic interventions.

RNA interference-mediated knockdown of CD49e (α5 integrin chain) in human thymic epithelial cells modulates the expression of multiple genes and decreases thymocyte adhesion

Abstract Background The thymus is a central lymphoid organ, in which bone marrow-derived T cell precursors undergo a complex process of maturation. Developing thymocytes interact with thymic microenvironment in a defined spatial order. A component of thymic microenvironment, the thymic epithelial cells, is crucial for the maturation of T-lymphocytes through cell-cell contact, cell matrix interactions and secretory of cytokines/chemokines. There is evidence that extracellular matrix molecules play a fundamental role in guiding differentiating thymocytes in both cortical and medullary regions of the thymic lobules. The interaction between the integrin α5β1 (CD49e/CD29; VLA-5) and fibronectin is relevant for thymocyte adhesion and migration within the thymic tissue. Our previous results have shown that adhesion of thymocytes to cultured TEC line is enhanced in the presence of fibronectin, and can be blocked with anti-VLA-5 antibody. Results Herein, we studied the role of CD49e expressed by the human thymic epithelium. For this purpose we knocked down the CD49e by means of RNA interference. This procedure resulted in the modulation of more than 100 genes, some of them coding for other proteins also involved in adhesion of thymocytes; others related to signaling pathways triggered after integrin activation, or even involved in the control of F-actin stress fiber formation. Functionally, we demonstrated that disruption of VLA-5 in human TEC by CD49e-siRNA-induced gene knockdown decreased the ability of TEC to promote thymocyte adhesion. Such a decrease comprised all CD4/CD8-defined thymocyte subsets. Conclusion Conceptually, our findings unravel the complexity of gene regulation, as regards key genes involved in the heterocellular cell adhesion between developing thymocytes and the major component of the thymic microenvironment, an interaction that is a mandatory event for proper intrathymic T cell differentiation.

Sequence features responsible for intron retention in human

Abstract Background One of the least common types of alternative splicing is the complete retention of an intron in a mature transcript. Intron retention (IR) is believed to be the result of intron, rather than exon, definition associated with failure of the recognition of weak splice sites flanking short introns. Although studies on individual retained introns have been published, few systematic surveys of large amounts of data have been conducted on the mechanisms that lead to IR. Results TTo understand how sequence features are associated with or control IR, and to produce a generalized model that could reveal previously unknown signals that regulate this type of alternative splicing, we partitioned intron retention events observed in human cDNAs into two groups based on the relative abundance of both isoforms and compared relevant features. We found that a higher frequency of IR in human is associated with individual introns that have weaker splice sites, genes with shorter intron lengths, higher expression levels and lower density of both a set of exon splicing silencers (ESSs) and the intronic splicing enhancer GGG. Both groups of retained introns presented events conserved in mouse, in which the retained introns were also short and presented weaker splice sites. Conclusion Although our results confirmed that weaker splice sites are associated with IR, they showed that this feature alone cannot explain a non-negligible fraction of events. Our analysis suggests that cis-regulatory elements are likely to play a crucial role in regulating IR and also reveals previously unknown features that seem to influence its occurrence. These results highlight the importance of considering the interplay among these features in the regulation of the relative frequency of IR.

Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth

Abstract Background Human Papillomavirus, HPV, is the main etiological factor for cervical cancer. Different studies show that in women infected with HPV there is a positive correlation between lesion grade and number of infiltrating macrophages, as well as with IL-10 higher expression. Using a HPV16 associated tumor model in mice, TC-1, our laboratory has demonstrated that tumor infiltrating macrophages are M2-like, induce T cell regulatory phenotype and play an important role in tumor growth. M2 macrophages secrete several cytokines, among them IL-10, which has been shown to play a role in T cell suppression by tumor macrophages in other tumor models. In this work, we sought to establish if IL-10 is part of the mechanism by which HPV tumor associated macrophages induce T cell regulatory phenotype, inhibiting anti-tumor activity and facilitating tumor growth. Results TC-1 tumor cells do not express or respond to IL-10, but recruit leukocytes which, within the tumor environment, produce this cytokine. Using IL-10 deficient mice or blocking IL-10 signaling with neutralizing antibodies, we observed a significant reduction in tumor growth, an increase in tumor infiltration by HPV16 E7 specific CD8 lymphocytes, including a population positive for Granzyme B and Perforin expression, and a decrease in the percentage of HPV specific regulatory T cells in the lymph nodes. Conclusions Our data shows that in the HPV16 TC-1 tumor mouse model, IL-10 produced by tumor macrophages induce regulatory phenotype on T cells, an immune escape mechanism that facilitates tumor growth. Our results point to a possible mechanism behind the epidemiologic data that correlates higher IL-10 expression with risk of cervical cancer development in HPV infected women.