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The article delves into the intersection of anthropology and literature, emphasizing how recent theoretical work has enriched the dialogue between these fields by exploring themes such as art, religion, subjectivity, and ethics, while also addressing methodological concerns. It highlights a series of conversations between fiction writer Siddratul Muntaha Jillani and anthropologist Kiran Nazir Ahmed, focusing on the parallels and contrasts between fiction writing and ethnographic writing.

Copyright of Humanidades: Revista de la Universidad de Montevideo is the property of Universidad de Montevideo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The C-terminal-binding protein 1/brefeldin A ADP-ribosylation substrate (CtBP1/BARS) acts both as an oncogenic transcriptional co-repressor and as a fission inducing protein required for membrane trafficking and Golgi complex partitioning during mitosis, hence for mitotic entry. CtBP1/BARS overexpression, in multiple cancers, has pro-tumorigenic functions regulating gene networks associated with "cancer hallmarks" and malignant behavior including: increased cell survival, proliferation, migration/invasion, epithelial-mesenchymal transition (EMT). Structurally, CtBP1/BARS belongs to the hydroxyacid-dehydrogenase family and possesses a NAD(H)-binding Rossmann fold, which, depending on ligands bound, controls the oligomerization of CtBP1/BARS and, in turn, its cellular functions. Here, we proposed to target the CtBP1/BARS Rossmann fold with small molecules as selective inhibitors of mitotic entry and pro-tumoral transcriptional activities. Methods: Structured-based screening of drug databases at different development stages was applied to discover novel ligands targeting the Rossmann fold. Among these identified ligands, N-(3,4-dichlorophenyl)-4-{[(4-nitrophenyl)carbamoyl]amino}benzenesulfonamide, called Comp.11, was selected for further analysis. Fluorescence spectroscopy, isothermal calorimetry, computational modelling and site-directed mutagenesis were employed to define the binding of Comp.11 to the Rossmann fold. Effects of Comp.11 on the oligomerization state, protein partners binding and pro-tumoral activities were evaluated by size-exclusion chromatography, pull-down, membrane transport and mitotic entry assays, Flow cytometry, quantitative real-time PCR, motility/invasion, and colony assays in A375MM and B16F10 melanoma cell lines. Effects of Comp.11 on tumor growth in vivo were analyzed in mouse tumor model. Results: We identify Comp.11 as a new, potent and selective inhibitor of CtBP1/BARS (but not CtBP2). Comp.11 directly binds to the CtBP1/BARS Rossmann fold affecting the oligomerization state of the protein (unlike other known CtBPs inhibitors), which, in turn, hinders interactions with relevant partners, resulting in the inhibition of both CtBP1/BARS cellular functions: i) membrane fission, with block of mitotic entry and cellular secretion; and ii) transcriptional pro-tumoral effects with significantly hampered proliferation, EMT, migration/invasion, and colony-forming capabilities. The combination of these effects impairs melanoma tumor growth in mouse models. Conclusions: This study identifies a potent and selective inhibitor of CtBP1/BARS active in cellular and melanoma animal models revealing new opportunities to study the role of CtBP1/BARS in tumor biology and to develop novel melanoma treatments. [ABSTRACT FROM AUTHOR]

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics. The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences. [ABSTRACT FROM AUTHOR]

Copyright of Question (1669-6581) is the property of Universidad Nacional de La Plata and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Mono-ADP-ribosylating PARP enzymes are involved in the regulation of several cellular pathways, including cell cycle. The mono-ADP-ribosyltransferase PARP10 is frequently amplified in different tumor types, and has been shown to promote in vitro cellular proliferation and in vivo tumoral growth. The aim of our study was to investigate the role of PARP10 in the regulation of G2/M transition. We found that PARP10 is involved in the mono-ADP-ribosylation of Aurora-A, an important mitotic kinase, during the G2/M transition. Moreover, PARP10-catalyzed modification enhances the kinase activity of Aurora-A. Consistently, the depletion of PARP10 affects the timely recruitment of Aurora-A on centrosomes and mitotic spindle, causing a delay in mitotic entry. Our discovery provides novel details in the cellular functions exerted by PARP10. Intracellular mono-ADP-ribosyltransferases (mono-ARTs) catalyze the covalent attachment of a single ADP-ribose molecule to protein substrates, thus regulating their functions. PARP10 is a soluble mono-ART involved in the modulation of intracellular signaling, metabolism and apoptosis. PARP10 also participates in the regulation of the G1- and S-phase of the cell cycle. However, the role of this enzyme in G2/M progression is not defined. In this study, we found that genetic ablation, protein depletion and pharmacological inhibition of PARP10 cause a delay in the G2/M transition of the cell cycle. Moreover, we found that the mitotic kinase Aurora-A, a previously identified PARP10 substrate, is actively mono-ADP-ribosylated (MARylated) during G2/M transition in a PARP10-dependent manner. Notably, we showed that PARP10-mediated MARylation of Aurora-A enhances the activity of the kinase in vitro. Consistent with an impairment in the endogenous activity of Aurora-A, cells lacking PARP10 show a decreased localization of the kinase on the centrosomes and mitotic spindle during G2/M progression. Taken together, our data provide the first evidence of a direct role played by PARP10 in the progression of G2 and mitosis, an event that is strictly correlated to the endogenous MARylation of Aurora-A, thus proposing a novel mechanism for the modulation of Aurora-A kinase activity. [ABSTRACT FROM AUTHOR]

The Golgi Complex is the central hub in the endomembrane system and serves not only as a biosynthetic and processing center but also as a trafficking and sorting station for glycoproteins and lipids. In addition, it is an active signaling hub involved in the regulation of multiple cellular processes, including cell polarity, motility, growth, autophagy, apoptosis, inflammation, DNA repair and stress responses. As such, the dysregulation of the Golgi Complex-centered signaling cascades contributes to the onset of several pathological conditions, including cancer. This review summarizes the current knowledge on the signaling pathways regulated by the Golgi Complex and implicated in promoting cancer hallmarks and tumor progression. [ABSTRACT FROM AUTHOR]

The expensive maintenance of legacy systems leads companies to migrate such systems to modern architectures. Microservice architectural style has become a trend to modernize monolithic legacy systems. A microservice architecture consists of small, autonomous, and highly-independent services communicating by using lightweight network protocols. To support the designing of microservice architectures, recent studies have proposed either single or multi-objective approaches. In order to improve the effectiveness of existing approaches, we introduced toMicroservices that is a many-objective search-based approach to aid the identification of boundaries among services. In previous studies, we have focused on a qualitative evaluation of the applicability and adoption of the proposed approach from a practical point of view, thus the optimization process itself has not been investigated in depth. In this paper, we extend our previous work by performing a more in-depth analysis of our many-objective approach for microservice identification. We compare our approach against a baseline approach based on a random search using a set of performance indicators widely used in the literature of many-objective optimization. Our results are validated through a real-world case study. The study findings reveal that (i) the criteria optimized by our approach are interdependent and conflicting; and (ii) all candidate solutions lead to better performance indicators in comparison to random search. Overall, the proposed many-objective approach for microservice identification yields promising results, which shed light on insights for further improvements. [ABSTRACT FROM AUTHOR]

Search-based algorithms have been successfully employed in Product Line Architecture (PLA) design in the seminal approach named Multi-Objective Approach for Product-Line Architecture Design (MOA4PLA). This approach generates a set of alternative PLA designs, which optimize different architectural properties. In addition to these properties, the alternative PLA designs should have as few architectural smells as possible. Architectural smells can negatively impact PLA variability, PLA extensibility, SPL maintainability, and other non-functional attributes. However, one of the main findings of a previous study is that the tool that automates the application of MOA4PLA adversely introduces architectural smells in the automatically generated solutions. In this work, we present OPLA-Tool-ASP, which is a tool that implements guidelines to detect and prevent the architectural smells Unused Interface, Unused Brick, Concern Overload, and Link Overload in the context of MOA4PLA. An empirical study was carried out to assess the effectiveness of OPLA-Tool-ASP in preventing the aforementioned smells in the resulting PLA designs. The obtained results pointed out that the proposed tool is effective in both preventing the smells and improving the architectural properties selected for optimization. [ABSTRACT FROM AUTHOR]

Background This study identified Trypanosoma cruzi discrete typing units (DTUs) in maternal and infant specimens collected from two hospitals in Bolivia, using conventional genotyping and DTU-specific serotyping. Methods Specimens from 142 mothers were used, including 24 seronegative and 118 seropositive individuals; 29 women transmitted T. cruzi to their infants. Maternal and infant parasite loads were determined by quantitative real-time PCR. Maternal sera were tested with an in-house parasite lysate ELISA and serotyped by a lineage-specific peptide ELISA, targeting the trypomastigote small surface antigen (TSSA). Trypanosoma cruzi genotypes in infected infants were determined by a triple PCR-RFLP assay. Results All infant specimens were genotyped as TcV. Maternal parasite loads and absorbance values by the lysate ELISA were significantly higher for transmitters compared with non-transmitters. Among seropositive mothers, 65.3% had positive results by the TSSA II/V/VI peptide ELISA. No significant difference in reactivity to TSSA II/V/VI was observed for transmitters compared with non-transmitters (79.3% vs 60.7%, respectively). Conclusions Our findings reinforce the difficulty in obtaining sufficient sample numbers and parasite DNA to investigate the interaction between parasite genetics and the risk of congenital transmission and argue for the inclusion of DTU-specific serotyping in prospective studies. [ABSTRACT FROM AUTHOR]

Copyright of Grafía is the property of Universidad Autonoma de Colombia, Facultad de Ciencias Humanas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Search-based algorithms have been successfully employed in Product Line Architecture (PLA) design in the seminal approach named Multi-Objective Approach for Product-Line Architecture Design (MOA4PLA). This approach generates a set of alternative PLA designs, which optimize different architectural properties. In addition to these properties, the alternative PLA designs should have as few architectural smells as possible. Architectural smells can negatively impact PLA variability, PLA extensibility, SPL maintainability, and other non-functional attributes. However, one of the main findings of a previous study is that the tool that automates the application of MOA4PLA adversely introduces architectural smells in the automatically generated solutions. In this work, we present OPLA-Tool-ASP, which is a tool that implements guidelines to detect and prevent the architectural smells Unused Interface, Unused Brick, Concern Overload, and Link Overload in the context of MOA4PLA. An empirical study was carried out to assess the effectiveness of OPLA-Tool-ASP in preventing the aforementioned smells in the resulting PLA designs. The obtained results pointed out that the proposed tool is effective in both preventing the smells and improving the architectural properties selected for optimization. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Psychology (UNLP) / Revista de Psicología (UNLP) is the property of Facultad de Psicologia Universidad Nacional de La Plata and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Golgi complex (GC) has an essential role in the processing and sorting of proteins and lipids. The GC of mammalian cells is composed of stacks of cisternae connected by membranous tubules to create a continuous network, the Golgi ribbon, whose maintenance requires several core and accessory proteins. Despite this complex structural organization, the Golgi apparatus is highly dynamic, and this property becomes particularly evident during mitosis, when the ribbon undergoes a multistep disassembly process that allows its correct partitioning and inheritance by the daughter cells. Importantly, alterations of the Golgi structure are associated with a variety of physiological and pathological conditions. Here, we review the core mechanisms and signaling pathways involved in both the maintenance and disassembly of the Golgi ribbon, and we also report on the signaling pathways that connect the disassembly of the Golgi ribbon to mitotic entry and progression. [ABSTRACT FROM AUTHOR]

The architectural properties of product‐line architecture (PLA) design have been successfully optimised by multi‐objective genetic algorithms (GAs). Memetic algorithms (MAs) extend GA by adding a local search after the global search process. MA outperformed GA in the context of class modelling, software testing and the next release problem. However, no studies on the application of MAs for PLA design optimisation were found in the literature. In light of this, the authors performed an exploratory study, where MA was used to apply design patterns for a search‐based PLA design (SBPD) and achieved promising results. From the obtained results, they adjusted the MA‐based implementation. This study aims at investigating if the MA is more profitable to SBPD than GAs. Two empirical studies that involve four PLA designs were carried out for this task by varying the pair of objective functions. Empirical results show that MA achieved satisfactory solutions, despite being influenced by the original PLA design. [ABSTRACT FROM AUTHOR]

The mammalian Golgi apparatus is organized in the form of a ribbon‐like structure positioned near the centrosome. Despite its multimodular organization, the Golgi complex is characterized by a prominent structural plasticity, which is crucial during essential physiological processes, such as the G2 phase of the cell cycle, during which the Golgi ribbon must be "unlinked" into isolated stacks to allow progression into mitosis. Here we show that the Golgi‐associated protein GRASP65, which is well known for its role in Golgi stacking and ribbon formation, is also required for the organization of the microtubule cytoskeleton. GRASP65 is not involved in microtubule nucleation or anchoring. Instead, it is required for the stabilization of newly nucleated microtubules, leading to their acetylation and clustering of Golgi stacks. Ribbon formation and microtubule stabilization are both regulated by JNK/ERK‐mediated phosphorylation of S274 of GRASP65, suggesting that this protein can coordinate the Golgi structure with microtubule organization. In agreement with an important role, tubulin acetylation is strongly reduced during the G2 phase of the cell cycle, allowing the separation of the Golgi stacks. Thus, our data reveal a fundamental role of GRASP65 in the integration of different stimuli to modulate Golgi structure and microtubule organization during cell division. [ABSTRACT FROM AUTHOR]

The design of the product line architecture (PLA) is a difficult activity that can benefit from the application of design patterns and from the use of a search-based optimization approach, which is generally guided by different objectives related, for instance, to cohesion, coupling and PLA extensibility. The use of design patterns for PLAs is a recent research field, not completely explored yet. Some works apply the patterns manually and for a specific domain. Approaches to search-based PLA design do not consider the usage of these patterns. To allow such use, this paper introduces a mutation operator named "Pattern-Driven Mutation Operator" that includes methods to automatically identify suitable scopes and apply the patterns Strategy, Bridge and Mediator with the search-based approach multi-objective optimization approach for PLA. A metamodel is proposed to represent and identify suitable scopes to receive each one of the patterns, avoiding the introduction of architectural anomalies. Empirical results are also presented, showing evidences that the use of the proposed operator produces a greater diversity of solutions and improves the quality of the PLAs obtained in the search-based optimization process, regarding the values of software metrics. [ABSTRACT FROM AUTHOR]

Background: The detection of Trypanosoma cruzi genetic material in clinical samples is considered an important diagnostic tool for Chagas disease. We have previously demonstrated that PCR using clot samples yields greater sensitivity than either buffy coat or whole blood samples. However, phenol-chloroform DNA extraction from clot samples is difficult and toxic. The objective of the present study was to improve and develop a more sensitive method to recover parasite DNA from clot samples for the diagnosis of Chagas disease. Methodology/Principal findings: A total of 265 match pair samples of whole blood–guanidine (GEB) and clot samples were analyzed; 150 were from Chagas seropositive subjects. DNA was extracted from both whole blood-guanidine samples, using a previously standardized methodology, and from clot samples, using a newly developed methodology based on a combination of the FastPrep technique and the standard method for GEB extraction. A qPCR targeting the nuclear satellite sequences was used to compare the sample source and the extraction method. Of the 150 samples from Chagas positive individuals by serology, 47 samples tested positive by qPCR with DNA extracted by both GEB and clot, but an additional 13 samples tested positive only in DNA extracted from clot. No serology-negative samples resulted positive when tested by qPCR. Conclusions: The new methodology for DNA extraction from clot samples improves the molecular diagnosis of Chagas disease. [ABSTRACT FROM AUTHOR]

Copyright of Derecho y Ciencias Sociales is the property of Universidad Nacional de La Plata and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Golgi apparatus plays essential roles in the processing and sorting of proteins and lipids, but it can also act as a signalling hub and a microtubule-nucleation centre. The Golgi complex (GC) of mammalian cells is composed of stacks connected by tubular bridges to form a continuous membranous system. In spite of this structural complexity, the GC is highly dynamic, and this feature becomes particularly evident during mitosis, when the GC undergoes a multi-step disassembly process that allows its correct partitioning and inheritance by daughter cells. Strikingly, different steps of Golgi disassembly control mitotic entry and progression, indicating that cells actively monitor Golgi integrity during cell division. Here, we summarise the basic mechanisms and the molecular players that are involved in Golgi disassembly, focussing in particular on recent studies that have revealed the fundamental signalling pathways that connect Golgi inheritance to mitotic entry and progression. [ABSTRACT FROM AUTHOR]

Background. Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect >50% of infected neonates, and 9-month follow-up is low. Methods. Women who presented for delivery at 2 urban hospitals in Santa Cruz Department, Bolivia, were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR), and immunoglobulin (Ig)M trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month and by IgG serology at 6 and 9 months. Results. Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot, and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1%, and 16.7%/100%, respectively. When birth and 1-month results were combined, cumulative sensitivities reached 84.2%, 73.7%, and 34.2%, respectively. Low birthweight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. Conclusions. The proportion of T. cruzi-infected infants with clinical signs has fallen since the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings. [ABSTRACT FROM AUTHOR]

Copyright of La Manzana de la discordia is the property of Universidad del Valle and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Subtle morphological changes and molecular alterations have been reported in normal-appearing tissue in prostates with high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). The severity and the distribution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to investigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa. Karyometry was performed on the whole-mount histological sections of three radical prostatectomy (RP) specimens. Two concentrical lines, one corresponding to the outer surface (or capsule) of the prostate and the other corresponding to one centimeter towards the center, were drawn with a black pen on each whole-mount section. The part of the prostate tissue between these two boundaries was then divided into twelve equal sectors or regions. The part within the inner line was divided into two regions. The analysis was also performed on the slides of the apex and base of the prostate. One prostate contained normal-looking epithelium only (case no. 1). Another contained both high-grade PIN and PCa, the former occupying larger areas than the latter (case no. 2). Both high-grade PIN and PCa were present in the third sample, in which PCa was more widely distributed than PIN (case no. 3). The lesion measured in each region was always the most severe, e.g., either high-grade PIN or PCa. When neither were identifiable, then the normal-looking columnar epithelium was analyzed. For each sector, the mean and standard deviation of the nuclear area, maximum nuclear diameter, nuclear roundness factor, and nucleolar area were calculated. In normal-looking columnar epithelium, the mean of the mean nuclear area of the sectors of case no. 1 was 35.19 µm2 (SD 4.14). The mean nuclear areas in cases no. 2 and no. 3 were 37.94 µm2 (SD 4.65) and 37.31 µm2 (SD 4.36), respectively. The mean of the mean nuclear area of the sectors with high-grade PIN of case no. 2 was 49.85 µm2 (SD 8.44), whereas it was 54.26 µm2 (SD 2.91) in case no. 3. The mean of the nuclear area values obtained in the sectors of cases no. 2 and no. 3 with PCa was 56.74 µm2 (SD 6.56) and 61.17 µm2 (SD 8.13), respectively. When considering the normal-looking tissue of the second and third case, 79% and 90%, respectively, of the regions showed nuclear area values greater than 34.94 µm2 (e.g., the 50th percentile of the mean nuclear area values of the regions of the first case). Sectors with normal-looking epithelium, whose nuclear area was above this threshold, were both adjacent to and at a distance of more than 1 cm from those with PIN or PCa. The other nuclear features showed a similar trend of value changes. This study demonstrates that the normal-looking ducts and acini from prostate harboring preneoplastic and neoplastic lesions show morphological nuclear abnormalities that are not seen by the human eyes but that can be detected with image analysis. Such changes may be of diagnostic importance, especially in cases where clinical suspicion for cancer prevails after a negative biopsy. [ABSTRACT FROM AUTHOR]

Various grading systems have been proposed for renal cell carcinoma (RCC), using nuclear, cytoplasmic, and architectural features. The available evidence suggests that nuclear grading is a better prognostic indicator than other types of grading schemes. Nuclear morphometry may still improve the correlation of the nuclear grading with survival, however, because observer consistency is lacking in the subjective grading of RCC. The aim of this study was to investigate morphometrically whether RCC cases show a continuous spectrum of nuclear changes or whether there are discrete groups of cancer that correspond to the four Fuhrman grades. Karyometry was performed on 5- µm-thick, haematoxylin- and eosin-stained sections from 60 cases of conventional (clear cell) RCC. The analysis also included the evaluation of normal renal tissue (proximal tubules) adjacent to cancer. In each case the difference between the value of the cancer and the corresponding normal epithelium was calculated to represent, quantitatively, the degree of similarity between the tumour tissue and the internal normal control. When the differences were sorted into ascending order, a steady increase in values was observed for both the nuclear and the nucleolar features. A monotonic trend was evident for the differences in the mean maximum nuclear diameter and mean nucleolar area. When the differences between the values in the cancer and in the corresponding normal epithelium of these two features were summed up, the method resulted in a continuous variable, or nuclear morphometric index, related to the degree of deviation of each individual RCC from its internal normal control. The lowest index values were observed in of Fuhrman grade I cases, whereas values ranging from 2.679 to 5.422 were associated with cases graded II. Values equal to or higher than 5.951 were seen in the cases assigned to either grade III or grade IV. Partial overlap was present between the index values in grades III and IV. The RCC cases can be represented by a continuous index that corresponds to the morphological grading based on the Fuhrman scheme. This study shows that the index may be useful in supplementing the pathologist’s grading. This issue can be further addressed with follow-up studies. [ABSTRACT FROM AUTHOR]

Background: We studied women and their infants to evaluate risk factors for congenital transmission and cardiomyopathy in Trypanosoma cruzi-infected women. Methods: Women provided data and blood for serology and quantitative polymerase chain reaction (PCR). Infants of infected women had blood tested at 0 and 1 month by microscopy, PCR and immunoblot, and serology at 6 and 9 months. Women underwent electrocardiography (ECG). Results: Of 1696 women, 456 (26.9%) were infected; 31 (6.8%) transmitted T. cruzi to their infants. Women who transmitted had higher parasite loads than those who did not (median, 62.0 [interquartile range {IQR}, 25.8-204.8] vs 0.05 [IQR, 0-29.6]; P < .0001). Transmission was higher in twin than in singleton births (27.3% vs 6.4%; P = .04).Women who had not lived in infested houses transmittedmore frequently (9.7% vs 4.6%; P=.04), weremore likely to have positive results by PCR (65.5% vs 33.9%; P < .001), and had higher parasite loads than those who had lived in infested houses (median, 25.8 [IQR, 0-64.1] vs 0 [IQR, 0-12.3]; P < .001). Of 302 infected women, 28 (9.3%) had ECG abnormalities consistent with Chagas cardiomyopathy; risk was higher for older women (odds ratio [OR], 1.06 [95% confidence interval {CI}, 1.01-1.12] per year) and those with vector exposure (OR, 3.7 [95% CI, 1.4-10.2]). We observed a strong doseresponse relationship between ECG abnormalities and reported years of living in an infested house. Conclusions: We hypothesize that repeated vector-borne infection sustains antigen exposure and the consequent inflammatory response at a higher chronic level, increasing cardiac morbidity, but possibly enabling exposed women to control parasitemia in the face of pregnancy-induced Th2 polarization. [ABSTRACT FROM AUTHOR]

Many pathogenic bacteria utilize ADP-ribosylating toxins to modify and impair essential functions of eukaryotic cells. It has been previously reported that Neisseria meningitidis possesses an ADP-ribosyltransferase enzyme, NarE, retaining the capacity to hydrolyse NAD and to transfer ADP-ribose moiety to arginine residues in target acceptor proteins. Here we show that upon internalization into human epithelial cells, NarE gains access to the cytoplasm and, through its ADP-ribosylating activity, targets host cell proteins. Notably, we observed that these events trigger the disruption of the epithelial monolayer integrity and the activation of the apoptotic pathway. Overall, our findings provide, for the first time, evidence for a biological activity of NarE on host cells, suggesting its possible involvement in Neisseria pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Congenital transmission is a major source of new Trypanosoma cruzi infections, and as vector and blood bank control continue to improve, the proportion due to congenital infection will grow. A major unanswered question is why reported transmission rates from T. cruzi-infected mothers vary so widely among study populations. Women with high parasite loads during pregnancy are more likely to transmit to their infants, but the factors that govern maternal parasite load are largely unknown. Better understanding of these factors could enable prioritization of screening programs to target women most at risk of transmission to their infants. Methodology/Principal Findings: We screened pregnant women presenting for delivery in a large urban hospital in Bolivia and followed infants of infected women for congenital Chagas disease. Of 596 women screened, 128 (21.5%) had confirmed T. cruzi infection; transmission occurred from 15 (11.7%) infected women to their infants. Parasite loads were significantly higher among women who transmitted compared to those who did not. Congenital transmission occurred from 31.3% (9/29), 15.4% (4/26) and 0% (0/62) of women with high, moderate and low parasite load, respectively (χx2 for trend 18.2; p<0.0001). Twin births were associated with higher transmission risk and higher maternal parasite loads. Infected women without reported vector exposure had significantly higher parasite loads than those who had lived in an infested house (median 26.4 vs 0 parasites/mL; p<0.001) with an inverse relationship between years of living in an infested house and parasite load. Conclusions/Significance: We hypothesize that sustained vector-borne parasite exposure and repeated superinfection by T. cruzi may act as an immune booster, allowing women to maintain effective control of the parasite despite the down-regulation of late pregnancy. [ABSTRACT FROM AUTHOR]

Background: Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc−) individuals. Methods: Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc− groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed. Results: Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities. Conclusions: BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes. Author Summary: In Chagas disease, a parasitic disease found primarily in Central and South America, individuals are chronically infected with the parasite Trypanosoma cruzi. A few decades after initial infection, 20–30% of infected individuals will develop cardiac disease. If we were able to predict which individuals would progress to cardiac disease, treatment in these low resource areas could be targeted to those at highest risk. The ideal transition point to identify those at risk would be as individuals progress from a normal electrocardiogram to an abnormal electrocardiogram, the first step in the progression of cardiac disease. Previous studies have suggested a group of serum biomarkers able to differentiate between these stages of disease. However, our larger and more comprehensive study finds that none of the ten cardiac and remodeling biomarkers we tested are able to distinguish between healthy individuals and those with the earliest evidence of cardiac disease. We did find cardiac biomarkers to be elevated in those with severe cardiac disease as expected in both T. cruzi infected and uninfected individuals. [ABSTRACT FROM AUTHOR]

Background: Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc−) individuals. Methods: Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc− groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed. Results: Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities. Conclusions: BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes. [ABSTRACT FROM AUTHOR]

An excerpt from the book "Vacaciones Permanentes," by Liliana Colanzi, translated by Heather Cleary, is presented, depicting the life of a foreign worker in England.