Trypanosoma cruzi DNA replication includes the sequential recruitment of pre-replication and replication machineries close to nuclear periphery

In eukaryotes, many nuclear processes are spatially compartmentalized. Previously, we have shown that in Trypanosoma cruzi, an early-divergent eukaryote, DNA replication occurs at the nuclear periphery where chromosomes remain constrained during the S phase of the cell cycle. We followed Orc1/Cdc6, a pre-replication machinery component and the proliferating cell nuclear antigen (PCNA), a component of replication machinery, during the cell cycle of this protozoon. We found that, at the G(1) stage, TcOrc1/Cdc6 and TcPCNA are dispersed throughout the nuclear space. During the G(1)/S transition, TcOrc1/Cdc6 migrates to a region close to nuclear periphery. At the onset of S phase, TcPCNA is loaded onto the DNA and remains constrained close to nuclear periphery. Finally, in G(2), mitosis and cytokinesis, TcOrc1/Cdc6 and TcPCNA are dispersed throughout the nuclear space. Based on these findings, we propose that DNA replication in T. cruzi is accomplished by the organization of functional machineries in a spatial-temporal manner.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Universidade Federal de São Paulo, Parasitol Lab, Inst Butantan, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Celular Hertha Meyer, BR-21941 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Parasitol Lab, Inst Butantan, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilWeb of Scienc

Overview of the Morphology of Neotropical Termite Workers: History and Practice

This contribution deals with the worker caste of the Neotropical termite fauna. It is a compilation of present knowledge about the morphology of pseudergates and workers, including the literature discussing the origin and evolution of this caste, the terminology used in the different taxonomic groups, and the techniques used to study these individuals, especially examination of the gut, mandibles, legs, and nota. In order to assist in identifying workers, it includes a key for the families that occur in the Neotropical Region and a characterization of workers of all families, especially the subfamilies of Termitidae, with descriptions and illustrations of diagnostic morphological features of genera. We point out advances and gaps in knowledge, as well as directions for future research

Is urinary density an adequate predictor of urinary osmolality?

Urinary density (UD) has been routinely used for decades as a surrogate marker for urine osmolality (U-osm). We asked if UD can accurately estimate U-osm both in healthy subjects and in different clinical scenarios of kidney disease. UD was assessed by refractometry. U-osm was measured by freezing point depression in spot urines obtained from healthy volunteers (N = 97) and in 319 inpatients with acute kidney injury (N = 95), primary glomerulophaties (N = 118) or chronic kidney disease (N = 106). UD and U-osm correlated in all groups (p < 0.05). However, a wide range of U-osm values was associated with each UD value. When UD was <= 1.010, 28.4% of samples had U-osm above 350 mOsm/kg. Conversely, in 61.6% of samples with UD above 1.020, U-osm was below 600 mOsm/kg. As expected, U-osm exhibited a strong relationship with serum creatinine (S-creat), whereas a much weaker correlation was found between UD and Screat. We found that UD is not a substitute for U-osm. Although UD was significantly correlated with U-osm, the wide dispersion makes it impossible to use UD as a dependable clinical estimate of U-osm. Evaluation of the renal concentrating ability should be based on direct determination of U-osm1

Central Auditory Processing Outcome After Stroke In Children.

To investigate central auditory processing in children with unilateral stroke and to verify whether the hemisphere affected by the lesion influenced auditory competence. 23 children (13 male) between 7 and 16 years old were evaluated through speech-in-noise tests (auditory closure); dichotic digit test and staggered spondaic word test (selective attention); pitch pattern and duration pattern sequence tests (temporal processing) and their results were compared with control children. Auditory competence was established according to the performance in auditory analysis ability. Was verified similar performance between groups in auditory closure ability and pronounced deficits in selective attention and temporal processing abilities. Most children with stroke showed an impaired auditory ability in a moderate degree. Children with stroke showed deficits in auditory processing and the degree of impairment was not related to the hemisphere affected by the lesion.72680-

Molecular imaging to identify patients with metastatic breast cancer who benefit from endocrine treatment combined with cyclin-dependent kinase inhibition

BACKGROUND: Adding cyclin-dependent kinase (CDK) inhibitor to endocrine treatment improves outcome in œstrogen receptor (ER) positive metastatic breast cancer, but identifying the subset of patients who benefit is challenging. Response is potentially associated with ER expression heterogeneity. This is because, unlike the primary tumour in the breast that is localized to the organ, the metastatic breast cancer has spread and continues to spread to distant locations in the body such as bones, lungs, liver, axial skeleton, even to the central nervous system like the brain, wherefrom obtaining biopsies are not easy, and also, the metastasised tissues are heterogeneous. Positron emission tomography (PET) with 16α-[18F]fluoro-17β-œstradiol (FES), briefly referred to as FES-PET, allows whole-body ER assessment. We explored whether FES-PET heterogeneity and FES uptake were related to letrozole and palbociclib outcome, in patients with ER positive, metastatic breast cancer. PATIENTS AND METHODS: Patients underwent a baseline FES-PET and 18F-fluorodeoxyglucose (FDG) PET, the FDG-PET served to help identify active sites of breast cancer with contrast-enhanced computed tomography (CT). FES-PET heterogeneity score (% FES positive lesions divided by all lesions on FDG-PET and/or CT) and FES uptake were related to outcome and 8-week FDG-PET response. Circulating tumour DNA (CtDNA) samples for ESR1 mutation analysis were collected at baseline. RESULTS: In 30 patients with 864 metastatic lesions, baseline FES-PET heterogeneity was assessed. In 27 patients with 688 lesions, response was evaluated. Median time to progression (TTP) was 73 weeks (95% confidence interval [CI] 21 to ∞) in 7 patients with 100% FES positive disease, 27 weeks (14-49) in heterogeneous FES positive disease (20 patients), and 15 weeks (9 to ∞) without FES positivity (three patients; log-rank P = 0.30). Geometric mean FES uptake was 2.3 for metabolic progressive patients, 2.5 (Pvs progression = 0.82) for metabolic stable disease, and 3.3 (Pvs progression = 0.40) for metabolic response (Ptrend = 0.21). ESR1 mutations, found in 13/23 patients, were unrelated to FES uptake. CONCLUSION: This exploratory study suggests that FES-PET heterogeneity may potentially identify the subset of ER positive, metastatic breast cancer patients who benefit from letrozole combined with CDK inhibition. CLINICAL TRIAL INFORMATION: NCT02806050

Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: a Multicase-Control Study in Spain (MCC-Spain)

Background: Chronic lymphocytic leukemia (CLL) etiology is poorly understood, and carcinogenic chemicals in drinking and recreational water are candidates. Objective: To evaluate the association between drinking-water exposure to trihalomethanes (THMs) and nitrate as well as lifetime swimming pool attendance and CLL. Methods: During 2010-2013, hospital-based CLL cases and population-based controls were recruited in Spain, providing information on residential histories, type of water consumed and swimming pool attendance. Average THMs and nitrate levels in drinking water were linked to lifetime water consumption. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models. Results: Final samples for residential tap water analyses and swimming pool attendance analyses were 144 cases/1230 controls and 157 cases/1240 controls, respectively. Mean (SD) values for average lifetime residential brominated THMs and chloroform in tap water (μg/L), and ingested nitrate (mg/day) were 48.1 (35.6), 18.5 (6.7) and 13.7 (9.6) respectively in controls; and 72.9 (40.7), 17.9 (5.4), and 14.1 (8.8) in CLL cases. For each 10 μg/L increase of brominated THMs and chloroform lifetime-average levels, the ORs (95% CI) were 1.22 (1.14, 1.31) and 0.54 (0.34, 0.87), respectively. For each 5 mg/day increase of ingested nitrate, the OR of CLL was 0.91 (0.80, 1.04). The OR of lifetime pool users (vs. non-users) was 2.38 (1.61, 3.52). Upon performing annual frequency of attending pools analysis through categorization, the second and third categories showed an ORs of 2.36 (1.49, 3.72) and 2.40 (1.51, 3.83), respectively, and P-trend of 0.001. Impact statement: This study identifies an association of long-term exposure to THMs in drinking water, at concentrations below the regulatory thresholds and WHO guidelines, and swimming pool attendance, with chronic lymphocytic leukemia (CLL). These unprecedented findings are highly relevant since CLL is an incurable cancer with still unknown etiology and because the widespread exposure to chlorination by-products that remain in drinking and recreational water worldwide. Despite the demonstrated carcinogenicity in animals of several chlorination by-products, little is known about their potential risks on human health. This study makes a significant contribution to the search for environmental factors involved in the etiology of CLL and to the evidence of the health impact of these high prevalent water contaminants.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01889, PI11/00226, PI12/01270, PI12/00715, PI14/0613, PI15/00914, PI17CIII/00034), by the Fundación Marqués de Valdecilla (API 10/09), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723, 2021SGR01354 and 2014SGR850, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.S

Efecto de la inoculación con bacterias promotoras del crecimiento vegetal en plantas de maíz (Zea mays L.) = Effect of inoculation with plant growth promoting bacteria in corn plants (Zea mays L.)

A pesar de que existen numerosos estudios de la interacción entre plantas de maíz (Zea mays) con Azospirillum brasilense, los reportes de la interacción con Gluconacetobacter diazotrophicus son escasos. El objetivo de este trabajo fue evaluar el efecto de la inoculación con microorganismos promotores del crecimiento vegetal correspondientes a las especies bacterianas de A. brasilense REC3 y G. diazotrophicus PAL5 sobre el desarrollo de plantas de maíz. Se implementaron ensayos en los que los microorganismos fueron inoculados en forma individual y conjunta en plantas de la variedad Leales 25 de maíz, las cuales fueron sembradas en dos suelos con distintos grados de fertilidad. Las variables medidas en las plantas fueron los valores relativos de SPAD (Soil Plant Analysis Development) y la longitud y superficie radicular. Los resultados obtenidos revelaron que A. brasilense REC3 y G. diazotrophicus PAL5 tuvieron efectos superiores a los tratamientos control y mezcla, y que sólo A. brasilense REC3 generó incrementos significativos en la biomasa en las plantas de maíz respecto a los demás tratamientos en ambos tipos de suelos.Although there are numerous studies of the interaction between corn plants (Zea mays) with Azospirillum brasilense, reports about the interaction with Gluconacetobacter diazotrophicus are scarce. The aim of this work was to evaluate the effect of inoculation with microorganisms that promote plant growth corresponding to the bacterial species of A. brasilense REC3 and G. diazotrophicus PAL5 on the development of maize plants. Trials were carried out in which the microorganisms were inoculated individually or in combination in corn plants of the variety Leales 25, which were sowed in two soils with different degrees of fertility. Variables measured in plants were relative values of Soil Plant Analysis Development (SPAD) and length and root surface. Results revealed that A. brasilense REC3 and G. diazotrophicus PAL5 had superior effects than the control. Only A. brasilense REC3 generated a significant increment in biomass of corn plants compared to other treatments in both types of soils.EEA FamailláFil: Lovaisa, Nadia Carolina. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; Argentina.Fil: Guevara, E.E. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Delaporte Quintana, Paola Adriana Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Elías, J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Arroyo, J. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; Argentina.Fil: Salazar, Sergio Miguel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; Argentina. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; Argentin

Informal “Seed” Systems and the Management of Gene Flow in Traditional Agroecosystems: The Case of Cassava in Cauca, Colombia

Our ability to manage gene flow within traditional agroecosystems and their repercussions requires understanding the biology of crops, including farming practices' role in crop ecology. That these practices' effects on crop population genetics have not been quantified bespeaks lack of an appropriate analytical framework. We use a model that construes seed-management practices as part of a crop's demography to describe the dynamics of cassava (Manihot esculenta Crantz) in Cauca, Colombia. We quantify several management practices for cassava—the first estimates of their kind for a vegetatively-propagated crop—describe their demographic repercussions, and compare them to those of maize, a sexually-reproduced grain crop. We discuss the implications for gene flow, the conservation of cassava diversity, and the biosafety of vegetatively-propagated crops in centers of diversity. Cassava populations are surprisingly open and dynamic: farmers exchange germplasm across localities, particularly improved varieties, and distribute it among neighbors at extremely high rates vis-à-vis maize. This implies that a large portion of cassava populations consists of non-local germplasm, often grown in mixed stands with local varieties. Gene flow from this germplasm into local seed banks and gene pools via pollen has been documented, but its extent remains uncertain. In sum, cassava's biology and vegetative propagation might facilitate pre-release confinement of genetically-modified varieties, as expected, but simultaneously contribute to their diffusion across traditional agroecosystems if released. Genetically-modified cassava is unlikely to displace landraces or compromise their diversity; but rapid diffusion of improved germplasm and subsequent incorporation into cassava landraces, seed banks or wild populations could obstruct the tracking and eradication of deleterious transgenes. Attempts to regulate traditional farming practices to reduce the risks could compromise cassava populations' adaptive potential and ultimately prove ineffectual

Assessment of Bone Lesions with F-18-FDG PET Compared with Tc-99m Bone Scintigraphy Leads to Clinically Relevant Differences in Metastatic Breast Cancer Management

It is unknown whether assessment of potential bone lesions in metastatic breast cancer (MBC) by F-18-FDG PET instead of Tc-99m bone scintigraphy (BS) supports clinically relevant changes in MBC management. Therefore, we retrospectively compared management recommendations based on bone lesion assessment by (18)FFDG PET plus contrast-enhanced CT (ceCT) or BS plus ceCT, for patients with newly diagnosed MBC. Methods: Baseline ceCT, BS, and F-18-FDG PET for all patients included in the IMPACT-MBC study (NCT01957332) at the University Medical Center Groningen were reviewed for bone lesions. If bone lesions were found by any imaging modality, virtual MBC management recommendations were made by a multidisciplinary expert panel, based on either F-18-FDG PET plus ceCT or BS plus ceCT. The panel had access to standard clinicopathologic information and baseline imaging findings outside the skeleton. Clinically relevant management differences between the 2 recommendations were defined either as different treatment intent (curative, noncurative, or unable to determine) or as different systemic or local treatment. If no bone lesions were found by any imaging modality, the patients were included in the analyses without expert review. Results: In total, 3,473 unequivocal bone lesions were identified in 10(2) evaluated patients (39% by ceCT, 26% by BS, and 87% by F-18-FDG PET). Additional bone lesions on F-18-FDG PET plus ceCT compared with BS plus ceCT led to change in MBC management recommendations in 16% of patients (95% CI, 10%-24%). BS also changed management compared with F-18-FDG PET in 1 patient (1%; 95% CI, 0%-5%). In 26% (95% CI, 19%-36%) of patients, an additional F-18-FDG PET exam was requested, because BS provided insufficient information. Conclusion: In this exploratory analysis of newly diagnosed MBC patients, F-18-FDG PET versus BS to assess bone lesions resulted in clinically relevant management differences in 16% of patients. BS delivered insufficient information in over one fourth of patients, resulting in an additional request for F-18-FDG PET. On the basis of these data, F-18-FDG PET should be considered a primary imaging modality for assessment of bone lesions in newly diagnosed MBC

Is urinary density an adequate predictor of urinary osmolality?

Abstract\ud \ud Background\ud Urinary density (UD) has been routinely used for decades as a surrogate marker for urine osmolality (Uosm). We asked if UD can accurately estimate Uosm both in healthy subjects and in different clinical scenarios of kidney disease.\ud \ud \ud Methods\ud UD was assessed by refractometry. Uosm was measured by freezing point depression in spot urines obtained from healthy volunteers (N = 97) and in 319 inpatients with acute kidney injury (N = 95), primary glomerulophaties (N = 118) or chronic kidney disease (N = 106).\ud \ud \ud Results\ud UD and Uosm correlated in all groups (p < 0.05). However, a wide range of Uosm values was associated with each UD value. When UD was ≤ 1.010, 28.4% of samples had Uosm above 350 mOsm/kg. Conversely, in 61.6% of samples with UD above 1.020, Uosm was below 600 mOsm/kg. As expected, Uosm exhibited a strong relationship with serum creatinine (Screat), whereas a much weaker correlation was found between UD and Screat.\ud \ud \ud Conclusion\ud We found that UD is not a substitute for Uosm. Although UD was significantly correlated with Uosm, the wide dispersion makes it impossible to use UD as a dependable clinical estimate of Uosm. Evaluation of the renal concentrating ability should be based on direct determination of Uosm