Gene polymorphism in five target genes of immunosuppressive therapy and risk of development of preeclampsia

Pregnancy can be considered as an allogeneic transplant and preeclampsia can be seen as a failure of the acceptance mechanisms of this transplant as occurs in acute organ transplant rejection. Some genetic polymorphisms may be involved in its pathogenesis. Since the kidney is one of the organs mainly involved in preeclampsia, our study attempted to determine the frequencies of single nucleotide polymorphisms of DNA (SNP) in 3 genes (adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1)/multi drug reactivity 1 (MDR1) gene, interleukin 10 gene and tumor necrosis factor \u3b1 gene) which are targets of immunosuppressive therapies and related to acute renal rejection. The study was an observational, monocentric, case-control study. We enrolled 20 women with severe preeclampsia and 10 women age-matched with regular pregnancy. Continuous variables were compared by the Student\u2019s t-test for independent variables or using the Mann-Whitney test depending on their distribution. We used Fisher test to compare categorical variables between cases and controls, while we used logistic regression model to evaluate which risk factor was associated with preeclampsia. Although there was no statistically significant difference between the two groups, we found different percentages of two of the polymorphisms considered (rs1045642 and rs2032582 in the gene ABCB1). Despite these results, our work may be helpful for future research to better understand the pathogenesis of preeclampsia

Hallazgo de tiburones cretácicos (Chondrichthyes) en la provincia de Mendoza (Argentina): aspectos estratigráficos y paleoambientales

Se comunica el hallazgo de dientes de tiburones cretácicos en la provincia de Mendoza, región septentrional de la Cuenca Neuquina, Argentina. Los restos, colectados entre los años 2001-2009, provienen de los niveles basales de la Formación Jagüel aflorantes en el anticlinal de Ranquil-Có, Sierra de Palauco, sur del Departamento de Malargüe. En ese sector los estratos cretácicos de los Grupos Neuquén y Malargüe afloran completos desde su base a techo y se encuentran plegados formando un anticlinal asimétrico. Desde la base de la Formación Loncoche (Campaniano superior-?Maastrichtiano inferior) hasta los niveles superiores de la suprayente Formación Jagüel (Maastrichtiano superior), el registro de vertebrados e invertebrados fósiles, como así también los análisis sedimentológicos, muestran una progresiva influencia marina vinculada con una ingresión procedente del Atlántico. Los dientes encontrados se asignan a los géneros Squalicorax Whitley y Serratolamna Landemaine (Elasmobranchii, Lamniformes). El género Squalicorax es típico del Cretácico Superior y no se conoce en el Cenozoico. Las facies portadoras de los dientes son margas y pelitas gris amarillentas. El estudio palinológico de cinco niveles de estas facies dio como resultado una asociación dominada casi exclusivamente por ficomas de algas prasinofíceas principalmente pertenecientes a los géneros: Pterospermella Eisenack, Cymatiosphaera Wetzel ex Deflandre y Tasmanites Newton, junto a escasos quistes de dinoflagelados y ausencia de palinomorfos terrestres. Estas algas son más frecuentes en ambientes marinos de reducida salinidad, como la zona proximal de plataforma y son abundantes en aguas preferentemente frías. El hallazgo aquí descripto amplía el escaso registro de condrictios del Cretácico de América del Sur austral y confirma el carácter marino de estas facies, lo que es congruente con el registro palinológico.Sesiones libresFacultad de Ciencias Naturales y Muse

Ultrasound approach as integration of gross anatomy educational path for medical students

For physicians, the human body is the focus of investigation and intervention on a daily basis. It follows that the study of anatomy will continue to be essential to safe medical practice [1]. Anatomical education represents the cultural path that includes the best coexistence of old techniques, and avant-garde. Thus teachers forming future physicians are imposed to find new strategies for the acquisition of adequate professional competences [2]. The gross anatomy course attended by medical students was integrated by ultrasound training. Students were trained either in palpating and recognizing surface body-landmarks, or in the detection of different viscera. Their abilities were then evaluated. For three academic years (since 2009-10 to 2011-12), all the 262 students enrolled in the first year of Medicine and Surgery degree (\u201cSan Paolo\u201d Hospital, Universit\ue0 degli Studi di Milano, Italy) participated. Of them, 16 volunteered in 2009-10, and 17 in each of the next two years, to preliminarily attend ultrasound training that their fellows would attend later. After this preliminary training, volunteers tutored their course fellows as peer tutors. All participants were either models or users. Each training presented three modules: 1) information about ultrasound scanning; 2) musculoskeletal system, major arterial and venous vessels, major nervous trunks, thyroid gland; 3) most thoracic, abdominal and pelvic viscera. Modules 2 and 3 were attended by small groups (6 students, assisted by 2 peer tutors). In module 2, topographical anatomy and subsequent recognition and palpation of surface bodylandmarks were also taught. The study of musculoskeletal system, major vessels and nerve trunks, and thyroid gland was supported by a multi-frequency probe equipped ultrasound machine. Thoracic, abdominal, and pelvic viscera were explored by a new generation pocket-sized ultrasound machine. Acquired skills were verified. The levels of expertise obtained by peer tutors and students were generally satisfactory. Students understood the importance of operative knowledge in human anatomical context. Anatomists found a valid method to consolidate the professionalizing quality of the topic

The effect of Young's modulus on the neuronal differentiation of mouse embryonic stem cells

There is substantial evidence that cells produce a diverse response to changes in ECM stiffness depending on their identity. Our aim was to understand how stiffness impacts neuronal differentiation of embryonic stem cells (ESC's), and how this varies at three specific stages of the differentiation process. In this investigation, three effects of stiffness on cells were considered; attachment, expansion and phenotypic changes during differentiation. Stiffness was varied from 2 kPa to 18 kPa to finally 35 kPa. Attachment was found to decrease with increasing stiffness for both ESC's (with a 95% decrease on 35 kPa compared to 2 kPa) and neural precursors (with a 83% decrease on 35 kPa). The attachment of immature neurons was unaffected by stiffness. Expansion was independent of stiffness for all cell types, implying that the proliferation of cells during this differentiation process was independent of Young's modulus. Stiffness had no effect upon phenotypic changes during differentiation for mESC's and neural precursors. 2 kPa increased the proportion of cells that differentiated from immature into mature neurons. Taken together our findings imply that the impact of Young's modulus on attachment diminishes as neuronal cells become more mature. Conversely, the impact of Young's modulus on changes in phenotype increased as cells became more mature

UEV-1 Is an Ubiquitin-Conjugating Enzyme Variant That Regulates Glutamate Receptor Trafficking in C. elegans Neurons

The regulation of AMPA-type glutamate receptor (AMPAR) membrane trafficking is a key mechanism by which neurons regulate synaptic strength and plasticity. AMPAR trafficking is modulated through a combination of receptor phosphorylation, ubiquitination, endocytosis, and recycling, yet the factors that mediate these processes are just beginning to be uncovered. Here we identify the ubiquitin-conjugating enzyme variant UEV-1 as a regulator of AMPAR trafficking in vivo. We identified mutations in uev-1 in a genetic screen for mutants with altered trafficking of the AMPAR subunit GLR-1 in C. elegans interneurons. Loss of uev-1 activity results in the accumulation of GLR-1 in elongated accretions in neuron cell bodies and along the ventral cord neurites. Mutants also have a corresponding behavioral defect—a decrease in spontaneous reversals in locomotion—consistent with diminished GLR-1 function. The localization of other synaptic proteins in uev-1-mutant interneurons appears normal, indicating that the GLR-1 trafficking defects are not due to gross deficiencies in synapse formation or overall protein trafficking. We provide evidence that GLR-1 accumulates at RAB-10-containing endosomes in uev-1 mutants, and that receptors arrive at these endosomes independent of clathrin-mediated endocytosis. UEV-1 homologs in other species bind to the ubiquitin-conjugating enzyme Ubc13 to create K63-linked polyubiquitin chains on substrate proteins. We find that whereas UEV-1 can interact with C. elegans UBC-13, global levels of K63-linked ubiquitination throughout nematodes appear to be unaffected in uev-1 mutants, even though UEV-1 is broadly expressed in most tissues. Nevertheless, ubc-13 mutants are similar in phenotype to uev-1 mutants, suggesting that the two proteins do work together to regulate GLR-1 trafficking. Our results suggest that UEV-1 could regulate a small subset of K63-linked ubiquitination events in nematodes, at least one of which is critical in regulating GLR-1 trafficking

No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age

Background : we investigated the association between 9 polymorphisms of genes encoding hemostasis factors and myocardial infarction in a large sample of young patients chosen because they have less coronary atherosclerosis than older patients, and thus their disease is more likely to be related to a genetic predisposition to a prothrombotic state Methods and Results : this nationwide case-control study involved 1210 patients who had survived a first myocardial infarction at an age of 45 years who underwent coronary arteriography in 125 coronary care units and 1210 healthy subjects matched for age, sex, and geographical origin. None of the 9 polymorphisms of genes encoding proteins involved in coagulation (G-455A -fibrinogen: OR, 1.0; CI, 0.8 to 1.2; G1691A factor V: OR, 1.1; CI, 0.6 to 2.1; G20210A factor II: OR, 1.0; CI, 0.5 to 1.9; and G10976A factor VII: OR, 1.0; CI, 0.8 to 1.3), platelet function (C807T glycoprotein Ia: OR, 1.1; CI, 0.9 to 1.3; and C1565T glycoprotein IIIa: OR, 0.9; CI, 0.8 to 1.2), fibrinolysis (G185T factor XIII: OR, 1.2; CI, 0.9 to 1.6; and 4G/5G plasminogen activator inhibitor type 1: OR, 0.9; CI, 0.7 to 1.2), or homocysteine metabolism (C677T methylenetetrahydrofolate reductase: OR, 0.9; CI, 0.8 to 1.1) were associated with an increased or decreased risk of myocardial infarction Conclusions : this study provides no evidence supporting an association between 9 polymorphisms of genes encoding proteins involved in hemostasis and the occurrence of premature myocardial infarction or protection against it

Ecomorphology and bone microstructure of Proterochampsia from the Chanares Formation

Proterochampsians are a South American endemic group of non-archosaurian archosauriforms with morphological characteristics recollecting Recent crocodilians, and therefore have been proposed as aquatic species. However, this has not been based on careful examination of anatomical and histological features. We provide a review of the morphological and histological evidence present in the skeleton of proterochampsids and discuss its implications for inferring the lifestyles of these organisms. Anatomical features such as a secondary palate, marginal dentition, palatine teeth, morphology of the tail, limb modification, and dermal armor are reviewed, and details of histological structures are described based on bone thin sections. Histological examination reveals a predominance of fibrolamellar bone tissue, suggesting rapid periosteal osteogenesis and therefore overall fast bone growth. The existence of discontinuities (LAGs) demonstrates that these animals responded to changes in their environment. Ecomorphological features do not provide definitive evidence for the lifestyles of proterochampsids, but allow us to propose a terrestrial/amphibious condition. The same is true of the histological features, particularly compactness of the bone

Le onde d'urto focali nella sindrome del piriforme

Il piriforme \ue8 un muscolo rotatore esterno dell\u2019anca che \ue8 coinvolto nella \u201csindrome del piriforme\u201d in quanto pu\uf2 causare dolore sia neuropatico, da compressione del nervo sciatico, sia da attivazione di trigger point miofasciali. La componente miofasciale di questa patologia comprende dolore al tratto lombare basso, alla regione glutea e alla parte posteriore della coscia ed \ue8 caratterizzata da un importante quadro di limitazione funzionale e disabilit\ue0 per il paziente. Le onde d\u2019urto focali sono in grado di indurre nel tessuto muscolare un immediato aumento della produzione locale di ossido nitrico e una successiva stimolazione della neoangiogenesi locale. Questi effetti lasciano ipotizzare un razionale impiego nelle sindromi da attivazione di trigger point miofasciali. Secondo il protocollo da noi predisposto, nei soggetti affetti da sindrome del piriforme somministriamo le onde d\u2019urto in tre sedute settimanali. \uc8 eseguita un\u2019attenta valutazione clinica prima del trattamento (T1), durante le sedute intermedie (T2-T3) e a un mese circa dall\u2019ultima seduta (T4). Le valutazioni comprendono: raccolta anamnestica, esame obiettivo caratterizzato da test clinici (Freiberg, Pace e Nagle, FAIR) e dall\u2019individuazione di trigger point attivi a livello del muscolo piriforme. Successivamente si procede alla somministrazione di due questionari per la valutazione della disabilit\ue0 e della limitazione funzionale dei pazienti (Roland-Morris e Oswestry Disabilty Index) e della Scala visiva analogica (VAS) per il dolore spontaneo. Utilizziamo un generatore di OU focali di tipo elettroidraulico con i seguenti parametri: 400 colpi per seduta (1200 colpi complessivi), profondit\ue0 20 mm, Frequenza 4Hz, energia totale circa 8,7 J. Le valutazioni dei pazienti trattati a T1, T2, T3 e T4 hanno mostrano un miglioramento clinico statisticamente significativo con progressiva diminuzione del dolore e della disabilit\ue0. Visti i risultati ottenuti, la sostanziale assenza di fattori di confondimento e di effetti collaterali, possiamo affermare che nei casi di sindrome del piriforme da attivazione di trigger point miofasciali le O. U. focali possono rappresentare un\u2019utile alterativa terapeutica