Miracle-dz/UniFAR-FTUs huggingface dataset:
How to use molecular marker data to measure evolutionary parameters in wild populations

Estimating the genetic basis of phenotypic traits and the selection pressures acting on them are central to our understanding of the evolution and conservation of wild populations. However, obtaining such evolutionary‐related parameters is not an easy task as it requires accurate information on both relatedness among individuals and their breeding success. Polymorphic molecular markers are very useful in estimating relatedness between individuals and parentage analyses are now extensively used in most taxa. The next step in the application of molecular data to wild populations is to use them to derive estimates of evolutionary‐related parameters for quantitative traits, such as quantitative genetic parameters (e.g. heritability, genetic correlations) and measures of selection (e.g. selection gradients). Despite their great appeal and potential, the optimal use of molecular tools is still debated and it remains unclear how they should best be used to obtain reliable estimates of evolutionary parameters in the wild. Here, we review the methods available for estimating quantitative genetic and selection parameters and discuss their merits and shortcomings, to provide a tool that summarizes the potential uses of molecular data to obtain such parameters in wild populations.
Actin cytoskeleton remodeling governs aquaporin‐4 localization in astrocytes

Aquaporin‐4 (AQP4) is constitutively concentrated in the plasma membrane of the perivascular glial processes, and its expression is altered in certain pathological conditions associated with brain edema or altered glial migration. When astrocytes are grown in culture, they lose their characteristic star‐like shape and AQP4 continuous plasma membrane localization observed in vivo. In this study, we differentiated primary astrocyte cultures with cAMP and lovastatin, both able to induce glial stellation through a reorganization of F‐actin cytoskeleton, and obtained AQP4 selectively localized on the cell plasma membrane associated with an increase in the plasma membrane water transport level, but only cAMP induced an increase in AQP4 total protein expression. Phosphorylation experiments indicated that AQP4 in astrocytes is neither phosphorylated nor a substrate of PKA. Depolymerization of F‐actin cytoskeleton performed by cytochalasin‐D suggested that F‐actin cytoskeleton plays a primary role for AQP4 plasma membrane localization and during cell adhesion. Finally, AQP4 knockdown does not compromise the ability of astrocytes to stellate in the presence of cAMP, indicating that astrocyte stellation is independent of AQP4. © 2008 Wiley‐Liss, Inc.
Identification of abrogated pathways in fallopian tube epithelium from BRCA1 mutation carriers

The discovery of occult invasive and intra‐epithelial tubal carcinomas in BRCA1 mutation carriers undergoing prophylactic surgery has implicated the fallopian tube epithelium as the source of serous cancer. However, little is known of the early molecular events of serous oncogenesis, or why cancers in BRCA1 mutation carriers are found preferentially in tissues which are responsive to reproductive hormones. We hypothesize that molecular alterations present in morphologically normal tubal epithelium from BRCA1 heterozygotes reflect the earliest events in serous carcinogenesis and may be markers of increased cancer risk as well as targets for risk reduction. Genetic profiling of microdissected tubal epithelium from histologically normal BRCA1 mutation carriers and controls was performed. We sought to define a signature which differentiated BRCA1 mutant tubal epithelium from women with low risk of developing ovarian cancer. Molecular differences between the follicular and luteal phases were prominent and, by using filtering techniques and a two‐way ANOVA without a False Discovery Rate correction, we identified 440 probe sets with a more than two‐fold change in gene expression related to BRCA1 mutation status. Using gene ontology and known associations to cancer pathways, we selected five genes for further analysis by qPCR and immunohistochemistry, and were able to demonstrate statistically significant differentiation of BRCA1 and control cases in an independent set of cases. The altered expression profiles in histologically normal tubal epithelium from BRCA1 heterozygotes suggest that these cells may respond differently to microenvironmental stresses. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma: analysis of prognostic factors.

AIM To review the surgical outcomes in terms of the surgical indications and relevant prognostic factors. METHODS Sixteen patients underwent therapeutic lung surgery between March 1999 and May 2006. The observation period was terminated on May 31, 2007. The surgical outcomes and the clinicopathological factors were compared. RESULTS There was no mortality or major morbidity encountered in this study. The mean follow-up period after metastasectomy was 26.7 +/- 28.2 (range: 1-99 mo), and the median survival time was 20 mo. The 1- and 5-year survival rates were 56% and 26%, respectively. At the end of the follow-up, 1 patient died from hepatic failure without recurrence, 6 died from hepatic failure with a recurrent hepatocellular carcinoma (HCC), and 4 died from recurrent HCC with cachexia. Among several clinical factors, Kaplan-Meier analysis revealed that liver transplantation as a treatment for the primary lesion, grade of cell differentiation, and negative evidence HBV infection were independent predictive factors. On Cox's proportional hazard model, there were no significant factors affecting survival after pulmonary metastasectomy in patients with HCC. CONCLUSION A metastasectomy should be performed before other treatments in selected patients. Although not significant, patients with liver transplantation of a primary HCC survived longer. Liver transplantation might be the most beneficial modality that can offer patients better survival. A multi-institutional and collaborative study would be needed for identifying clinical prognostic factors predicting survival in patients with HCC and lung metastasis.
Rate of Perihematomal Edema Expansion Predicts Outcome After Intracerebral Hemorrhage

Objectives:Intracerebral hemorrhage is a devastating disorder with no current treatment. Whether perihematomal edema is an independent predictor of neurologic outcome is controversial. We sought to determine whether perihematomal edema expansion rate predicts outcome after intracerebral hemorrhage. Design:Retrospective cohort study. Setting:Tertiary medical center. Patients:One hundred thirty-nine consecutive supratentorial spontaneous intracerebral hemorrhage patients 18 years or older admitted between 2000 and 2013. Interventions:None. Measurements and Main Results:Intracerebral hemorrhage, intraventricular hemorrhage, and perihematomal edema volumes were measured from CT scans obtained at presentation, 24-hours, and 72-hours postintracerebral hemorrhage. Perihematomal edema expansion rate was the difference between initial and follow-up perihematomal edema volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) perihematomal edema expansion rate at 24 hours and 90-day mortality and 2) perihematomal edema expansion rate at 24 hours and 90-day modified Rankin Scale score. Perihematomal edema expansion rate between admission and 24-hours postintracerebral hemorrhage was a significant predictor of 90-day mortality (odds ratio, 2.97; 95% CI, 1.48–5.99; p = 0.002). This association persisted after adjusting for all components of the intracerebral hemorrhage score (odds ratio, 2.21; 95% CI, 1.05–4.64; p = 0.04). Similarly, higher 24-hour perihematomal edema expansion rate was associated with poorer modified Rankin Scale score in an ordinal shift analysis (odds ratio, 2.40; 95% CI, 1.37–4.21; p = 0.002). The association persisted after adjustment for all intracerebral hemorrhage score components (odds ratio, 2.07; 95% CI, 1.12–3.83; p = 0.02). Conclusions:Faster perihematomal edema expansion rate 24-hours postintracerebral hemorrhage is associated with worse outcome. Perihematomal edema may represent an attractive translational target for secondary injury after intracerebral hemorrhage.
The Political Consequences of the Protests against Neo-Liberal Reforms in Nigeria: The Case of OccupyNigeria Movement

This paper analyses the mechanisms, outcomes, and consequences of the Nigerian protest movement using longitudinal qualitative research. To go about this, the paper looks at the protests in the context of neo-Liberal reforms, the essential trigger of the movement, its objectives, and its achievements are described. The movement started on January 2, 2012 as a direct response to the Nigerian government’s announcement of the commencement of fullscale deregulation of the downstream sector of the petroleum industry. The movement took public protests in Nigeria to a new level with lasting impacts on the political system. This paper observes the “non-institutional” mechanisms adopted by the protesters to achieve their objectives.
Up-Regulation of Protein Kinase C-ε Promotes the Expression of Cytokine-inducible Nitric Oxide Synthase in RAW 264.7 Cells*

Stimulation of the murine macrophage RAW 264.7 cell line with phorbol esters fails to promote nitric oxide synthesis as occurs in rat hepatocytes or peritoneal macrophages. Transfection of RAW 264.7 cells with plasmids harboring protein kinase C (PKC) -ε isotype but not with PKC-α, -β1, -δ, or constitutively active -α and -β1 isotypes resulted in the expression of nitric oxide synthase type II (iNOS), as reflected by the synthesis of nitric oxide measured in the culture medium of transfected cells. cotransfection of RAW 264.7 cells with the −1592 to +121-base pair promoter region of the murine iNOS gene and PKC isotypes specifically induced the transactivation of this promoter in the case of the plasmids containing the PKC-ε isotype. The mechanism by which PKC-ε induced iNOS expression involved the activation of nuclear factor binding to κB sites (NF-κB) as deduced by the suppressive effect of pyrrolidine dithiocarbamate on nitric oxide synthesis, an inhibitor of NF-κB activation, and by the activation of κB sites in cells transfected with a vector containing a κB motif linked to a chloramphenicol acetyltransferase reporter gene. These results suggest that PKC-ε can regulate a pathway that promotes iNOS expression in macrophages in response to phorbol ester activation.
Reconstruction of Absorbed Doses to Fibroglandular Tissue of the Breast of Women Undergoing Mammography (1960 to the Present)

The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters, including imaging protocols, X-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations that can be used in epidemiological studies of breast cancer.
MAJOR PATHOLOGIC FINDINGS AND PROBABLE CAUSES OF MORTALITY IN BOTTLENOSE DOLPHINS STRANDED IN SOUTH CAROLINA FROM 1993 TO 2006

Although cause-of-death information on bottlenose dolphins (Tursiops truncatus) can be located in the literature, few citations include mortality data over a long period of time covering a broad geographic region. This study describes major pathologic findings and probable causes of death of bottlenose dolphins over a 14-yr period (1993–2006) for the coastal region of South Carolina. Probable causes of death for 97 cases were determined based on gross pathology and histopathology. In an additional 30 cases, probable cause of death was apparent from gross pathology alone, and carcass condition precluded histopathology. Of the 97 dolphins examined grossly and histologically, 30 (31%) likely died of infectious disease and 46 (47%) of noninfectious disease; the cause of death was unknown in 21 (22%). Bacterial infections accounted for the large majority of fatal infections and emaciation was the leading cause of noninfectious mortality. Twelve dolphins were killed by human interactions. Of the 30 dolphins diagnosed from gross examination alone, 23 likely died from human interaction and seven were killed by stingray-spine inflictions. Although the absence of consistent use of microbiology, biotoxin analysis and contaminant testing decreases the conclusiveness of the findings, this study has broad implications in establishing baseline data on causes of death of bottlenose dolphins for future studies and for the detection of emerging diseases.
Revisiting the Environmental Kuznets Curve

The view that human released CO2 emissions are one of the main causes of anthropogenic global warming is now widespread among the scienti c community. Ranging from rising sea levels to land and water shortages the e ects of climate change on the global ecosystem and the world economy will be severe. This makes the existence of a U-shaped relationship between economic development and pollution the Holy Grail of environmental economics. While there is theoretical support for this so called Environmental Kuznets Curve (EKC), epirical evidence is far from robust, sometimes even contradicting theoretical suggestions. Here we test for the existence of an inverted U-shaped relationship between carbon dioxide emissions and real income for a panel of 78 individuals (66 countries and 12 composite regions) for the years 1997, 2001, 2004 and 2007. We contribute to the literature in two ways. First, by applying multi-region input output (MRIO) methodology on the GTAP database we can also take CO2 consumption into account besides established production-based measures. Secondly, we also apply a threshold model alongside conventional lniear models on our dataset. Applying the linear models we can adress methodological issues of the existing literature. Our results show a linear relationship between real income and the production and consumption of CO2 emissions. We have some support for the hypothesis that consumption of CO2 is indeed increasing with income, which we want to testify with an threshold approach. The existence or non-existence of an EKC for CO2 is of considerable importance of the design of global mitigation mechanisms and agreements on climate change.
Neurodevelopmental outcome of children born following assisted reproductive technology: 0-2 years

Background: The effect of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) on the developing human brain is unclear. The objective of this study is to evaluate neurodevelopmental (ND) outcome of children born following these techniques. Methods: This systematic review includes studies which compare a group of children born following IVF/ICSI to children born after natural conception by assessing outcome in terms of neuromotor development, cognition, speech/ language and behaviour. Specific attention is paid to the studies’ methodological quality based on study design, attrition, blinding of the assessor, validity of ND tests used, confounders included and group size or power analysis. Results: Twenty-three out of 59 studies had a good methodological quality including 9 register-based (RB) and 14 controlled studies. RB studies suggested that IVF/ ICSI per se does not increase the risk for severe cognitive impairment (i.e. mental retardation) or neuromotor handicaps such as cerebral palsy (CP), the association of IVF/ICSI and CP being brought about by the association of assisted conception with risk factors, like preterm birth. In general, controlled studies of good quality did not report an excess of ND disorders in IVF/ICSI-children. However, the majority of studies followed the children during infancy only, thereby precluding pertinent conclusions on the risk of ND disorders that come to the expression at older ages, such as fine manipulative disability or dyslexia. Conclusions: A negative effect of assisted conception on the developing human brain is not identified; however, further research of high methodological quality in children beyond pre-school age is needed.
The Significance of the Sulfatase Pathway for Local Estrogen Formation in Endometrial Cancer

Endometrial cancer (EC) is the most common estrogen-dependent gynecological malignancy in the developed World. To investigate the local formation of estradiol (E2), we first measured the concentrations of the steroid precursor androstenedione (A-dione) and the most potent estrogen, E2, and we evaluated the metabolism of A-dione, estrone-sulfate (E1-S), and estrone (E1) in cancerous and adjacent control endometrium. Furthermore, we studied expression of the key genes for estradiol formation via the aromatase and sulfatase pathways. A-dione and E2 were detected in cancerous and adjacent control endometrium. In cancerous endometrium, A-dione was metabolized to testosterone, and no E2 was formed. Both, E1-S and E1 were metabolized to E2, with increased levels of E2 seen in cancerous tissue. There was no significant difference in expression of the key genes of the aromatase (CYP19A1) and the sulfatase (STS, HSD17B1, HSD17B2) pathways in cancerous endometrium compared to adjacent control tissue. The mRNA levels of CYP19A1 and HSD17B1 were low, and HSD17B14, which promotes inactivation of E2, was significantly down-regulated in cancerous endometrium, especially in patients with lymphovascular invasion. At the protein level, there were no differences in the levels of STS and HSD17B2 between cancerous and adjacent control tissue by Western blotting, and immunohistochemistry revealed intense staining for STS and HSD17B2, and weak staining for SULT1E1 and HSD17B1 in cancerous tissue. Our data demonstrate that in cancerous endometrium, E2 is formed from E1-S via the sulfatase pathway, and not from A-dione via the aromatase pathway.
Crystal Structures of the Toll/Interleukin-1 Receptor (TIR) Domains from the Brucella Protein TcpB and Host Adaptor TIRAP Reveal Mechanisms of Molecular Mimicry*

Background: The Toll/IL-1 receptor (TIR) domains are crucial innate immune signaling modules. Results: The crystal structures of the TIR domains from TcpB and TIRAP reveal similar folds and distinct features. Conclusion: TcpB may mimic the function of TIRAP through their similar TIR domain structures. Significance: These findings suggest mechanisms of bacterial mimicry of host signaling adaptor proteins. The Toll/IL-1 receptor (TIR) domains are crucial innate immune signaling modules. Microbial TIR domain-containing proteins inhibit Toll-like receptor (TLR) signaling through molecular mimicry. The TIR domain-containing protein TcpB from Brucella inhibits TLR signaling through interaction with host adaptor proteins TIRAP/Mal and MyD88. To characterize the microbial mimicry of host proteins, we have determined the X-ray crystal structures of the TIR domains from the Brucella protein TcpB and the host adaptor protein TIRAP. We have further characterized homotypic interactions of TcpB using hydrogen/deuterium exchange mass spectrometry and heterotypic TcpB and TIRAP interaction by co-immunoprecipitation and NF-κB reporter assays. The crystal structure of the TcpB TIR domain reveals the microtubule-binding site encompassing the BB loop as well as a symmetrical dimer mediated by the DD and EE loops. This dimerization interface is validated by peptide mapping through hydrogen/deuterium exchange mass spectrometry. The human TIRAP TIR domain crystal structure reveals a unique N-terminal TIR domain fold containing a disulfide bond formed by Cys89 and Cys134. A comparison between the TcpB and TIRAP crystal structures reveals substantial conformational differences in the region that encompasses the BB loop. These findings underscore the similarities and differences in the molecular features found in the microbial and host TIR domains, which suggests mechanisms of bacterial mimicry of host signaling adaptor proteins, such as TIRAP.
Cytogenetic monitoring of hospital staff exposed to ionizing radiation: optimize protocol considering DNA repair genes variability

Abstract Purpose: Chronic occupational exposure to ionizing radiation (IR) induces a wide spectrum of DNA damages. The aim of this study was to assess the frequencies of micronucleus (MN), sister chromatid exchanges (SCE) and to evaluate their association with XRCC1 399 Arg/Gln and XRCC3 241 Thr/Met polymorphisms in Hospital staff occupationally exposed to IR. Materials and methods: A questionnaire followed by a cytogenetic analysis was concluded for each subject in our study. The exposed subjects were classified into two groups based on duration of employment (Group I < 15 years; Group II ≥15years). The genotypes of all individuals (subjects and controls) were determined by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Results: DNA damage frequencies were significantly greater in IR workers compared with controls (p < .05). However, no association arised between XRCC1 399 Arg/Gln and XRCC3 241 Thr/Met polymorphisms, on one hand, and the severity of DNA damages in the studied cohort of Tunisian population, on the other hand. Conclusion: Our data provide evidence for an obvious genotoxic effect associated with IR exposure and reinforce the high sensitivity of cytogenetic assays for biomonitoring of occupationally exposed populations. These results indicate that workers exposed to IR should have periodic monitoring, along their exposure. The variants, rs25487 and rs861539, of XRCC1 and XRCC3 genes have obvious functional effects. Paradoxically, these variants are not associated with the severity of damages, according to used assays, in the studied cohort of Tunisian population, unlike other studies.