bluuebunny/crossref_metadata_2025 huggingface dataset:
A metabolic modeling-based framework for predicting trophic dependencies in native rhizobiomes of crop plants
Authors: Ginatt Alon Avraham , Berihu Maria , Castel Einam , Medina Shlomit , Carmi Gon , Faigenboim-Doron Adi , Sharon Itai , Tal Ofir , Droby Samir , Somera Tracey , Mazzola Mark , Eizenberg Hanan , Freilich Shiri
Published: April 2024

The exchange of metabolites (i.e., metabolic interactions) between bacteria in the rhizosphere determines various plant-associated functions. Systematically understanding the metabolic interactions in the rhizosphere, as well as in other types of microbial communities, would open the door to the optimization of specific pre-defined functions of interest, and therefore to the harnessing of the functionality of various types of microbiomes. However, mechanistic knowledge regarding the gathering and interpretation of these interactions is limited. Here, we present a framework utilizing genomics and constraint based modeling approaches, aiming to interpret the hierarchical trophic interactions in the soil environment. 243 genome-scale metabolic models of bacteria associated with a specific disease suppressive vs disease conductive apple rhizospheres were drafted based on genome resolved metagenomes, comprising an
in-silico
native microbial community. Iteratively simulating microbial community members' growth in a metabolomics-based apple root-like environment produced novel data on potential trophic successions, used to form a network of communal trophic dependencies. Network-based analyses have characterized interactions associated with beneficial vs non-beneficial microbiome functioning, pinpointing specific compounds and microbial species as potential disease supporting and suppressing agents. This framework provides a means for capturing trophic interactions and formulating a range of testable hypotheses regarding the metabolic capabilities of microbial communities within their natural environment. Essentially, it can be applied to different environments and biological landscapes, elucidating the conditions for the targeted manipulation of various microbiomes, and the execution of countless predefined functions.
Robust estimation of cancer and immune cell-type proportions from bulk tumor ATAC-Seq data
Authors: Gabriel Aurélie AG , Racle Julien , Falquet Maryline , Jandus Camilla , Gfeller David
Published: April 2024

Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) is a widely used technique to explore gene regulatory mechanisms. For most ATAC-Seq data from healthy and diseased tissues such as tumors, chromatin accessibility measurement represents a mixed signal from multiple cell types. In this work, we derive reliable chromatin accessibility marker peaks and reference profiles for all major cancer-relevant cell types. We then capitalize on the EPIC deconvolution framework (Racle et al. 2017) previously shown to accurately predict cell-type composition in tumor bulk RNA-Seq data and integrate our markers and reference profiles to EPIC to quantify cell-type heterogeneity in bulk ATAC-Seq data. Our EPIC-ATAC tool accurately predicts non-malignant and malignant cell fractions in tumor samples. When applied to a breast cancer cohort, EPIC-ATAC accurately infers the immune contexture of the main breast cancer subtypes.
A Deep Learning Pipeline for Mapping in situ Network-level Neurovascular Coupling in Multi-photon Fluorescence Microscopy
Authors: Rozak Matthew , Mester James , Attarpour Ahmadreza , Dorr Adrienne , Patel Shruti , Koletar Margaret , Hill Mary , McLaurin JoAnne , Goubran Maged , Stefanovic Bojana
Published: April 2024

Functional hyperaemia is a well-established hallmark of healthy brain function, whereby local brain blood flow adjusts in response to a change in the activity of the surrounding neurons. Although functional hyperemia has been extensively studied at the level of both tissue and individual vessels, vascular network-level coordination remains largely unknown. To bridge this gap, we developed a deep learning-based computational pipeline that uses two-photon fluorescence microscopy images of cerebral microcirculation to enable automated reconstruction and quantification of the geometric changes across the microvascular network, comprising hundreds of interconnected blood vessels, pre and post-activation of the neighbouring neurons. The pipeline’s utility was demonstrated in the Thy1-ChR2 optogenetic mouse model, where we observed network-wide vessel radius changes to depend on the photostimulation intensity, with both dilations and constrictions occurring across the cortical depth, at an average of 16.1±14.3 μm (mean±stddev) away from the most proximal neuron for dilations; and at 21.9±14.6 μm away for constrictions. We observed a significant heterogeneity of the vascular radius changes within vessels, with radius adjustment varying by an average of 24 ± 28% of the resting diameter, likely reflecting the heterogeneity of the distribution of contractile cells on the vessel walls. A graph theory-based network analysis revealed that the assortativity of adjacent blood vessel responses rose by 152 ± 65% at 4.3 mW/mm
2
of blue photostimulation
vs
. the control, with a 4% median increase in the efficiency of the capillary networks during this level of blue photostimulation in relation to the baseline. Interrogating individual vessels is thus not sufficient to predict how the blood flow is modulated in the network. Our computational pipeline, to be made openly available, enables tracking of the microvascular network geometry over time, relating caliber adjustments to vessel wall-associated cells’ state, and mapping network-level flow distribution impairments in experimental models of disease.
Input-specific gating of NMDA amplification via HCN channels in mouse L2/3 pyramidal neurons
Authors: Oláh Viktor János , Wu Jing , Kaczmarek Leonard K , Rowan Matthew JM
Published: April 2024

Layer 2/3 pyramidal cells (L2/3 PCs) play a crucial role in cortical information transfer. Although the dendritic arbors of L2/3 PCs are impressive, they often lack the distinct anatomical compartments characteristic of deeper L5 PCs. For example, many L2/3 PCs do not display an apparent distal tuft region. However, L2/3 PCs receive inputs from both thalamic (bottom-up) and cortical (top-down) inputs, which preferentially synapse onto their proximal and distal dendrites, respectively. Nonuniform organization of channels and NMDA receptors in L2/3 dendrites could serve to independently modulate these information streams to affect learning and behavior, yet whether L2/3 PC dendrites possess this capability has not been established. Here we found a previously unappreciated, non-uniform HCN channel distribution in L2/3 PCs, allowing for pathway-specific gating of NMDA receptor recruitment at bottom-up (proximal) but not top-down (distal) synapses. HCN availability shifted depending on developmental stage and neuromodulation, suggesting that the gain of thalamic and cortical-cortical signals in L2/3 may be independently modified
in vivo
across different timescales.
‘Hidden’ HCN channels permit pathway-specific synaptic amplification in L2/3 pyramidal neurons
Authors: Oláh Viktor János , Wu Jing , Kaczmarek Leonard K. , Rowan Matthew JM
Published: April 2024

Layer 2/3 pyramidal cells (L2/3 PCs) play a crucial role in cortical information transfer. Although the dendritic arbors of L2/3 PCs are impressive, they lack the distinct anatomical compartments characteristic of deeper L5 PCs. For example, many L2/3 PCs do not display an apparent distal tuft region. However, L2/3 PCs receive inputs from both thalamic (bottom-up) and cortical (top-down) inputs, preferentially synapsing onto their proximal and distal dendrites, respectively. Nonuniform organization of channels and NMDA receptors in L2/3 dendrites could serve to independently modulate these information streams to affect learning and behavior, yet whether L2/3 PC dendrites possess this capability has not been established. Here, we found a previously unappreciated non-uniform HCN channel distribution in L2/3 PCs, allowing for pathway-specific gating of NMDA receptor recruitment at bottom-up (proximal) but not top-down (distal) synapses. Interestingly, HCN availability could be regulated via neuromodulation, suggesting that the gain of thalamic and cortical-cortical signals in L2/3 may be independently modified in vivo.
Artificially inserted G-quadruplex DNA secondary structures induce long-distance chromatin activation
Authors: Roy Shuvra Shekhar , Bagri Sulochana , Sengupta Avik , Then Claudia Regina , Kumar Rahul , Sridharan Sriram , Chowdhury Shantanu
Published: April 2024

Although the role of G-quadruplex (G4) DNA structures has been suggested in chromosomal looping this was not tested directly. Here, to test causal function, an array of G4s, or control sequence that does not form G4s, were inserted within chromatin in cells. Compared to the control insert, we observed a remarkable increase in the number of 3D chromatin looping interactions from the inserted G4 array. This was evident within the immediate topologically associated domain (TAD) and throughout the genome. Locally, recruitment of enhancer histone marks and the transcriptional coactivator p300/Acetylated-p300 increased in the G4-array, but not in the control insertion. Resulting promoter-enhancer interactions and gene activation were clear up to 5 Mb away from the insertion site. Together, these show the causal role of G4s in enhancer function and long-range chromatin interactions. Mechanisms of 3D topology are primarily based on DNA-bound architectural proteins that induce/stabilize long-range interactions. Involvement of the underlying intrinsic DNA sequence/structure in 3D looping shown here therefore throws new light on how long-range chromosomal interactions might be induced or maintained.
Implementando mejoras para el desarrollo del trabajo colaborativo docente en una escuela técnico profesional de la comuna de Maipú
Authors:   , Lara Urbina Leonardo Alejandro
Published: April 2024

El trabajo nace inspirado por las llamadas Redes De Mejoramiento Escolar (RME, Mineduc 2015). En este contexto, el proyecto tiene como propósito y objetivo general “fortalecer el trabajo colaborativo entre los docentes de la carrera de gastronomía e Inglés en un tercero medio en un Liceo Técnico Profesional de la comuna de Maipú. Para lo anterior se proponen tres objetivos específicos y el objetivo principal. La implementación del proyecto contempla capacitaciones, las cuales están inspiradas en workshops internacionales validadas por expertos nacionales. Para la mejor implementación del proyecto la metodología seleccionada fue el Design-Based Research, ya que permite testear intervenciones en contextos educativos reales. Los principales resultados de la intervención fueron: Trabajo colaborativo: Se logró transmitir eficazmente las bases del trabajo en equipo en el departamento de gastronomía, fortaleciendo la colaboración entre colegas y alumnos a través de la culminación exitosa de un proyecto. Liderazgo Distribuido: Se implementaron prácticas de liderazgo que promueven una perspectiva distribuida, fomentando un enfoque colaborativo en la toma de decisiones y la resolución de problemas dentro del departamento. Nuevas metodologías: La adquisición de metodologías como la Indagación Colaborativa y el Aprendizaje basado en Proyectos permitió abordar deficiencias mediante diferentes perspectivas y habilidades, promoviendo el trabajo cooperativo.
Genotoxicity and Cytotoxicity Activities of Stembark Extract of Mammea africana
Authors: Okokon Jude E. , Edet Elvis , Iyanyi Uchechukwu Loveth , Ebong Nwakaego O. , Anagboso Martin Osita , Johhny Imoh Imeh
Published: April 2024

Mammea africana, a medicinal plant, used in ethnomedicine for the treatment of malaria, diabetes, poisoning and inflammatory diseases was investigated for cytotoxic and genotoxic effects on the root meristem cells of Allium cepa. Onion bulbs were exposed to 2.5 mg/mL, 5mg/mL, and 10 mg/mL concentrations of the stembark extract for macroscopic and microscopic analysis. Tap water was used as a negative control and Methotrexate (0.1 mg/mL) as a positive control. There was statistically significant (p< 0.05) inhibition of root growth depending on concentration by the extract when compared with the negative control group. All the tested concentrations of the extract were observed to have cytotoxic effect on cell division in A. cepa. When compared to the control group, the extract-induced chromosomal abnormalities and micronuclei (MNC) forms in A. cepa root tip cells were substantial (p<0.05). Further inducing cell death, ghost cells, membrane damage, and binucleated cells was the extract treatment. These findings imply that the phytochemical components of Mammea africana root extract exert their cytotoxic and genotoxic actions on A. cepa.
Anal Melanoma: An Atypical Case
Authors: Saavedra-Hurtado L.G. , Ortiz-Sánchez I.D. , Galvan-Navarrete M.
Published: April 2024

When talking about "Melanoma" it is easy to think that it is a malignant tumor produced by the alteration of melanocytes, but we leave aside that there can also be melanomas in the mucous membrane, it is certainly an atypical presentation but not impossible. Now, a melanoma in the anal mucosa is still an atypical and unusual presentation, adding that its symptoms are variable, and can be confused with any other pathology, which makes its diagnosis difficult and impoverishes its prognosis as there is no early treatment.
We present the case of a woman in her sixth decade of life, with non-specific symptoms in the anal region. Being a rare case, it is right to emphasize its clinicopathological importance.
Management of Watersheds as a Planning, Monitoring and Evaluation Zone Unit for the Development of the City: A Case Study of Karangmumus Watershed at Samarinda City, East Kalimantan Province, Indonesia
Authors: Sujalu Akas Pinaringan
Published: April 2024

The changing land use affects the social and economic characteristics and environmental issues in a watershed. To support sub-watershed management, land use scenarios and the level of community involvement must be improved. This research is a study to analyse and evaluate the condition of the Karangmumus watershed covering 365.25 km2 which is mostly located in Samarinda City, the capital of East Kalimantan Province. Research was conducted with various sources of data analysed using descriptive quantitative methods. In assessing the condition of a watershed, it is absolutely necessary to have debit data and other data to support the analysis and evaluation. In reality, currently the quantity and quality of flow data is still far from expected. This is due to the difficulties that cause the flow data collection process can not be done in all places, but only in certain watersheds. In the watershed monitoring carried out, there are still obstacles, one of which is the continuity of observation.
Association between Facet Fluid on Supine Axial T2-Weighted MRI and Sagittal Instability on Dynamic Standing Lateral Radiographs in Patients with Degenerative Lumbar Disease
Authors: Nasir Sadaf , Hussain Manzar , Shamim Bushra , Shahab Fawwaz Bin , Ali Muhammad Yassar Jazaib
Published: April 2024

Study Design: Prospective observational study conducted at a large tertiary care center in Karachi, Pakistan.

Purpose: To examine the association between positive facet fluid on T2-weighted MRI of lumbosacral spine and the presence of instability on lateral flexion/extension radiographs, and to determine whether a correlation exists between the quantity of facet fluid on axial MRI and the degree of spinal instability on lateral standing flexion/extension radiographs.

Overview of literature: The presence of increased facet fluid on axial T2-weighted magnetic resonance imaging (MRI) has been proposed as a potential marker for motion segment instability in the lumbar spine. Both facet fluid on MRI and spinal instability on dynamic x-rays are crucial in diagnosing and managing low back pain, guiding decisions on surgical interventions.

Methods: We analyzed the prospectively collected data from patients meeting the inclusion criteria. Facet fluid measurements were made according to Schinnerer's criteria on axial T2-weighted images and anterior translation as a marker of instability was evaluated on dynamic radiographs for all eligible patients. Statistical analysis was performed using IBM SPSS version 23, employing cross-tabulations, chi-square tests, and Pearson correlation. The study utilized a null hypothesis to evaluate the association between facet fluid and spinal instability.

Results: Our findings demonstrated a statistically significant association between positive facet fluid on MRI and the occurrence of instability on lateral flexion/extension radiographs. Moreover, we found a strong positive correlation between the volume of facet fluid on axial MRI and the level of spinal instability on standing flexion/extension radiographs.

Conclusion: Based upon these outcomes, we propose that standing lateral flexion–extension radiographs should be routinely administered to patients exhibiting increased facet fluid signals on MRI, as they may provide valuable information regarding potential spinal instability. Further research will help establish the clinical utility of this approach in managing degenerative lumbar diseases.
Contemporary Agricultural Land Management Practices under Climate Change and Population Increase Scenarios: Insights from Tanzania’s Southern Highlands
Authors: Malekela Asnath Alberto , Sieber Stefan , Mapunda January , Chobo Jafari S
Published: April 2024

This study investigated the impact of population growth and climate change on land management practices. The study was conducted in Mbinga district located in the Southern Highlands of Tanzania. Quantitative and qualitative research approaches were employed. Research data were collected using structured questionnaires, in-depth interviews, physical observation, focus group discussions and literature review. A total of 267 household heads were selected for this study. Also, the study used climate data from Tanzania Meteorological Authority, temperature and rainfall data over the past 40 years were collected (1981-2021). The findings revealed that, the area has experienced increased population and climate change incidences. The trend line for both minimum and maximum temperatures indicate a substantial increased trends at (P= 0.0018, R2=0.0005; P=0.0176, R2=0.02359) respectively. Contrariwise, the area has experienced decrease in rainfall totals at (P= 0.4385, R2=0.0008). It was revealed that, various traditional methods of land management practices including the use of animal manures, mulching, fallowing and the use of crop residues were affected by population increase and climate change. Farmers adopted new agricultural practices including the use of industrial fertilizers and reducing the size of contour terraces as the coping strategies for agricultural production against environmental deterioration caused by population increase and climate change.  However, the sustainability of such practices is uncertain due to continued population increase and climate change scenarios. Therefore, the study recommends for introduction of sustainable land management practices that would instigate for sustainable food production for the changing population.
Gestão da Propriedade Intelectual em Núcleos de Inovação Tecnológica de Instituições de Ensino Superior: cenário nacional
Authors: Lazzarin Flávia Cristina , Santos Junior Elias Lira dos , Colla Eliane , Silva-Buzanello Rosana Aparecida da
Published: April 2024

As Instituições de Ensino Superior (IES) estão no cerne da produção de pesquisas científicas e tecnológicas com a capacidade de amplificar a Transferência de Tecnologia (TT), a colaboração com a indústria e a geração de impacto socioeconômico por meio da identificação e proteção adequada das inovações geradas no âmbito de suas atuações. Nesse contexto, o presente trabalho buscou identificar e categorizar práticas de gestão da Propriedade Intelectual (PI) em Núcleos de Inovação Tecnológica (NITs) nacionais. A pesquisa é classificada como descritiva em termos de objetivos e qualitativa em sua abordagem. Os resultados obtidos revelam que, apesar de os NITs das IES enfrentarem desafios significativos em termos de estrutura, recursos humanos e financeiros para a proteção adequada da PI, existem práticas de gestão implementadas por IES nacionais que têm se mostrado eficientes e eficazes. Espera-se que as práticas de gestão identificadas possam ser adaptadas para outros NITs que enfrentam desafios semelhantes.
Gestão da Propriedade Intelectual em Instituição de Ensino Superior: uma revisão da literatura
Authors: Nakamura Márcio Akio , Fedato Geovana Alves de Lima , Gasparini Liz Vanessa Lupi
Published: April 2024

A universidade é uma instituição com potencial para promover inovação em colaboração com governo e indústria no modelo de tripla hélice. Os ativos intelectuais criados no ambiente universitário, além de proteção, prescindem de um sistema de gestão. O objetivo desta pesquisa foi identificar e caracterizar as formas de gestão de Propriedade Intelectual (PI) propostas na literatura para Instituições de Ensino Superior (IES). O método utilizado foi de revisão sistemática da literatura com auxílio do Protocolo Prisma. Foram realizadas pesquisas na base de dados do periódico Capes e Scopus e selecionados nove artigos que compuseram o escopo da pesquisa. Os resultados demonstram que a gestão de PI envolve políticas externas e internas, favoráveis à inovação, sendo imprescindível o engajamento com os stakeholders. O gerenciamento da PI é realizado de várias formas, destacando-se a transferência de tecnologias por meio de escritórios. São utilizadas ferramentas como: benchmarking, cursos e treinamento de capacitação.
Educação Empreendedora: uma análise da metodologia do ensino de empreendedorismo no ensino médio do IFCE, Câmpus Cedro
Authors: Oliveira Tacialene Alves de , Braun Maria do Socorro  de Assis , Rocha Marcia Maria Maciel de Melo , Castro Suyane da Silva
Published: April 2024

A Educação Empreendedora (EE) é muito abrangente e pode aprimorar as formas de aprendizagens dos discentes. Por isso, é importante possibilitar ao aluno práticas e vivências que fazem parte do desenvolvimento do comportamento empreendedor. Desse modo, este estudo corresponde a um recorte da dissertação que aborda esse tema, com embasamento bibliográfico inspirado nos princípios das pedagogias de John Dewey, Paulo Freire e Joseph Schumpeter. Assim, esta pesquisa buscou investigar a metodologia utilizada no ensino do empreendedorismo no ensino médio integrado. O procedimento técnico utilizado foi um estudo de caso, com abordagem qualitativa e pesquisa participante, contendo fontes de dados primárias e secundárias, revisão bibliográfica e análise dos dados pesquisados. Os resultados apontam métodos de ensino tradicionais baseados principalmente na exposição de conteúdo, nas limitações de abordagens pedagógicas, nas temáticas, nas experiências práticas, na carga horária reduzida e nas vivências empreendedoras que podem ser aprimoradas para estimular os alunos.
Propriedade Intelectual nas Universidades e Institutos Federais da Região Norte: um mapeamento com foco em programas de computador, marcas e patentes
Authors: Senna Yanka Andrade , Oliveira Junior Manoel Carlos de
Published: April 2024

A Região Norte possui 11 Universidades Federais e sete Institutos Federais, abarcando áreas do conhecimento cujas produções são passíveis de proteção legal. O presente artigo analisa, entre 2012 e 2022, a atuação dessas instituições quanto ao desenvolvimento inovador e tecnológico, considerando: Programas de Computador e Marcas e Patentes. Quanto à metodologia, foram utilizados a análise documental, a pesquisa bibliográfica e a prospecção tecnológica junto ao Instituto Nacional da Propriedade Industrial (INPI) e a análise preditiva, utilizando a linguagem Python. A busca resultou em 39 Marcas, 550 Patentes e 301 Programas de Computador. A Universidade Federal do Pará se destaca com maior número de ativos de Propriedade Intelectual. Concluiu-se que o planejamento adequado dos NITs contribui para aumentar a proteção do conhecimento, como no caso da UFRA, da Unifap e da Ufopa. Entretanto, a análise preditiva mostra que não há tendência de crescimento, sendo necessárias ações que incentivem a proteção intelectual e o registro de marcas e softwares.
Patentes sobre Tecnologias Aplicadas ao Esporte
Authors: Miranda Karolina Ribeiro Paes Oliveira Benevides , Sampaio Romilson  Lopes , Teles Eduardo Oliveira , Ribeiro Nubia Moura
Published: April 2024

A tecnologia tem desempenhado um papel cada vez mais importante na inteligência esportiva nos últimos anos. Desde o uso de sensores e dispositivos nas vestimentas para monitorar o desempenho dos atletas em tempo real até o uso de dados e análises avançadas para entender melhor o jogo, a tecnologia tem mudado a maneira como os esportes são analisados. O objetivo deste trabalho foi a apresentar um mapeamento de patentes acerca de tecnologias aplicadas no esporte. Para alcançar esse objetivo, foi realizada uma prospecção de patentes na plataforma do Orbit Intelligence. Os dados indicam que em 2006 foi depositada a primeira patente relacionada à tecnologia e ao esporte e demonstram que o uso de ferramentas tecnológicas vem para contribuir na melhoria no desenvolvimento do esporte, do conhecimento científico, tecnológico, inovação e políticas esportivas.
Estudos Prospectivos das Tecnologias e Mercados Relacionados aos Peixes Ornamentais
Authors: Costa Marcela Fróes da , Mafra Rosana Zau , Barbalho Celia Regina
Published: April 2024

O artigo discute a temática sobre peixes ornamentais, tendo em vista sua importância para o mercado de piscicultura ornamental, atividade crescente no Brasil e no mundo. No Amazonas, a pesca de peixes ornamentais é reconhecida pela Indicação de Procedência (IP) Rio Negro. Foi realizado um levantamento sobre tecnologias e mercados relacionados ao tema em bases patentárias e comerciais e em literatura científica, identificando as tendências atuais e os potenciais avanços tecnológicos na área da piscicultura ornamental, além de uma entrevista. Como principal resultado, identificou-se que os países asiáticos dominam técnicas de manejo, reprodução em laboratório de diversas espécies não selvagens, além de tecnologias que auxiliam na saúde e manutenção da piscicultura ornamental. Os resultados contribuem com a gestão da IP Rio Negro, ao identificarem mercados e avanços tecnológicos que podem impulsionar a pesca ornamental, a fim de impulsionar a comercialização dos peixes ornamentais do estado do Amazonas.
Highly Efficient Molybdenum(II)‐Catalyzed Intramolecular Allylic Alkylation of Arenes
Authors: Bandini Marco , Eichholzer Astrid , Kotrusz Peter , Umani‐Ronchi Achille
Published: February 2008

The Friedel–Crafts‐type intramolecular allylic alkylation of simple arenes is performed in the presence of a catalytic amount of [Mo(II) (CO)4Br2]2 (2.5 mol%). The moisture‐tolerant protocol provided a mild and direct access to a large library of functionalized 4‐vinyl‐1,2,3,4‐tetrahydronaphthalenes in high yields.
Prevalence and risk factors for pulmonary artery systolic hypertension among sickle cell disease patients in Nigeria
Authors: Aliyu Zakari Y. , Gordeuk Victor , Sachdev Vandana , Babadoko Aliyu , Mamman Aisha I. , Akpanpe Peter , Attah Ester , Suleiman Yusuf , Aliyu Nurudeen , Yusuf Jamilu , Mendelsohn Laurel , Kato Gregory J. , Gladwin Mark T.
Published: February 2008

Pulmonary artery systolic hypertension is common and associated with increased mortality among adult sickle cell disease (SCD) patients in the United States. Although the prevalence of SCD is highest in sub‐Saharan Africa, the frequency of pulmonary artery systolic hypertension and the risk factors for the development of pulmonary hypertension have not been reported from Africa. We studied 208 hydroxyurea naïve Nigerian SCD patients at steady state and 94 healthy controls. Pulmonary artery systolic hypertension was defined prospectively as tricuspid regurgitant jet velocity ≥2.5 m/sec. Results were compared with a previously published US prospective SCD cohort. Only 7% of Nigerians compared with 46% of US adults with SCD were >35 years. Tricuspid regurgitant jet velocity was ≥2.5 m/sec in 25% of Nigerian SCD patients. Higher jet velocity was associated with greater serum globulin (P = 0.002), blood urea nitrogen (P = 0.019) and lactate dehydrogenase concentrations (P = 0.026) and with inability to walk >300 m in 6 min (P = 0.042). Compared with the US cohort, Nigerian patients had more hemolysis as indicated by lower hemoglobin and higher lactate dehydrogenase concentrations (P ≤ 0.003). Pulmonary hypertension is common among Nigerian SCD patients. The public health implication of this finding is significant considering the potential number of individuals at risk for this complication. Better understanding of the long term outcome of pulmonary hypertension and causes of death in SCD and the institution of preventive measures are major public health challenges for Africa. The inclusion of African sites in sickle cell pulmonary hypertension clinical trials should be encouraged. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Isolated extramedullary relapse presenting as autologous lymphocyte response
Authors: Imataki Osamu , Ohnishi Hiroaki , Kitanaka Akira , Kubota Yoshitsugu , Tanaka Terukazu , Ishida Toshihiko
Published: February 2008

Isolated EMR in the CNS is a relatively rare form of recurrent leukemia. We report here a case of a 38‐year‐old man with inv(16) acute myeloid leukemia (AML, M2) who suffered a central nervous system (CNS) relapse after allogeneic bone marrow transplantation (BMT) from a human leukocyte antigen (HLA)‐matched sibling donor. After complete remission was achieved by chemotherapy, he received allogeneic BMT from his HLA‐matched sister. His leukemia relapsed in the CNS 2.5 years after the allogeneic BMT. Lumbar puncture revealed 780/μL white blood cells with 67.3% leukemia cells and 32.7% mature lymphocytes. Fluorescent in situ hybridization (FISH) using a probe for the Y chromosome demonstrated that both leukemia cells and lymphocytes in the cerebrospinal fluid (CSF) were derived from the recipient, although the bone marrow cells were from the donor. No leukemia cells with inv(16) were detected by FISH in the bone marrow. This is the first report to clarify the chimerism of lymphocytes in the CSF of patients with isolated EMR in the CNS after allogeneic SCT, in which analysis revealed that autologous immunologic cells rather than donor lymphocytes responded to the recurrent isolated leukemic cells in CNS. This observation suggests that the CNS is a “sanctuary” site not only from chemotherapy but also from the graft‐versus‐leukemia effect. The present case contributes to our understanding of the possibility of immunological escape phenomenon of recurrent leukemia cells in extramedullary sites. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Plasma concentrations of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell patients but do not increase further during painful crisis
Authors: Landburg Precious P. , Teerlink Tom , Muskiet Frits A.J. , Duits Ashley J. , Schnog John‐John B.
Published: February 2008

Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in the clinically asymptomatic state of sickle cell disease (SCD). However, the role of ADMA during vaso‐occlusive complications has not been defined. ADMA concentrations were determined in HbSS (n = 43) and HbSC (n = 25) patients with healthy blood donors (HbAA) as controls. In the clinically asymptomatic state ADMA concentrations were elevated in sickle cell patients as compared to healthy controls (HbSS 0.70 μmol/L, HbSC 0.54 μmol/L, HbAA 0.39 μmol/L) (P < 0.001). Yet plasma ADMA concentrations did not increase further at presentation with a painful crisis implicating no role of primary importance during vaso‐occlusive crises. Am. J. Hematol. 2008. © 2008 Wiley‐Liss, Inc.
Transfusion‐related acute lung injury following intravenous anti‐D administration in an adolescent
Authors: Berger‐Achituv Sivan , Ellis Martin H. , Curtis Brian R. , Wolach Baruch
Published: February 2008

Transfusion‐related acute lung injury (TRALI) is associated with administration of all plasma containing blood products. We present a 14‐year‐old adolescent diagnosed with idiopathic thrombocytopenic purpura who developed acute respiratory insufficiency compatible with TRALI within 5 hr following intravenous anti‐D. Full blown noncardiogenic pulmonary edema was noted after 9 hr. Mechanical ventilation was not required and the patient made a full recovery after 36 hr. Analysis of the anti‐D preparation revealed reactivity against the neutrophil FcγRIIIb. A postinfusion serum sample contained antibodies against class I human HLA‐A11 antigen. Clinicians should consider TRALI in patients developing unexplained dyspnea after receiving intravenous anti‐D. Am. J. Hematol. 2008. © 2008 Wiley‐Liss, Inc.
Familial interstitial deletion of the short arm of chromosome 4 (p15.33–p16.3) characterized by molecular cytogenetic analysis
Authors: Basinko Audrey , Douet‐Guilbert Nathalie , Parent Philippe , Blondin Gilles , Mingam M. , Monot Françoise , Morel Frédéric , Le Bris Marie‐Josée , De Braekeleer Marc
Published: February 2008

This 15‐month boy was expressed at the cytogenetic laboratory because of psychomotor development delay. He was tall and had plagiocephaly, micrognathia, high nasal bridge, anteverted nostrils and pectus excavatum. A 46,XY,del(4)(p16.1p16.3) karyotype was found using high‐resolution R‐banding technique. FISH studies using the LSI Wolf–Hirschhorn dual color 4p16.3 and the TelVysion 4p probes showed no deletion. Using BACs, the distal breakpoint was located in 4p16.3, between RP11‐165K4 and RP11‐717M10 and the proximal breakpoint in 4p15.33, between RP11‐74M11 and RP11‐1J7; therefore, approximately 7.96 Mb of the short arm were deleted. The maternal karyotype showed the same deletion, but in a mosaic status. Two distinct phenotypes have been recognized on the basis of the chromosomal bands involved in 4p deletion: the Wolf–Hirschhorn syndrome (WHS) and a proximal 4p deletion syndrome (4p15.2–p15.32). Our observation confirms that the basic WHS phenotype maps distally to this region. © 2008 Wiley‐Liss, Inc.
Dysferlin‐deficient muscular dystrophy features amyloidosis
Authors: Spuler Simone , Carl Miriam , Zabojszcza Joanna , Straub Volker , Bushby Kate , Moore Steven A. , Bähring Sylvia , Wenzel Katrin , Vinkemeier Uwe , Rocken Christoph
Published: February 2008

Objective

Dysferlin (DYSF) gene mutations cause limb girdle muscular dystrophy type 2B and Miyoshi's myopathy. The consequences of DYSF mutations on protein structure are poorly understood.

Methods

The gene encoding dysferlin was sequenced in patients with suspected dysferlin‐deficient muscular dystrophy. Muscle biopsy specimens were analyzed by histochemistry, immunohistochemistry, and electron microscopy. Antibodies against N‐terminal dysferlin‐peptides were raised.

Results

We found three families with muscular dystrophy caused by homozygous or compound heterozygous DYSF mutations featuring sarcolemmal and interstitial amyloid deposits. These mutations were all located in the N‐terminal region of the protein. Dysferlin was a constituent of the amyloid deposits.

Interpretation

Limb girdle muscular dystrophy type 2B is the first muscular dystrophy associated with amyloidosis. Molecular treatment strategies will necessarily have to consider the presence of amyloidogenesis. Ann Neurol 2008
Lesion distribution in children with clinically isolated syndromes
Authors: Ghassemi Rezwan , Antel Samson B. , Narayanan Sridar , Francis Simon J. , Bar‐Or Amit , Sadovnick A. Dessa , Banwell Brenda , Arnold Douglas L. ,   Canadian Pediatric Demyelinating Disease Study Group
Published: February 2008

We evaluated the incidence, volume, and spatial distribution of T2‐weighted magnetic resonance imaging lesions in 58 children with clinically isolated syndromes at risk for multiple sclerosis compared with 58 adults with relapsing‐remitting multiple sclerosis. Pediatric patients with clinically isolated syndromes who had brain lesions had supratentorial lesion volumes similar to adult multiple sclerosis patients, but greater infratentorial lesion volumes (p < 0.009), particularly in the pons of male patients. The predilection for infratentorial lesions the pediatric patients with clinically isolated syndromes may reflect immunological differences or differences in myelin, possibly related to the caudorostral temporal gradient in myelin maturation. Ann Neurol 2008
Muscle 3243A→G mutation load and capacity of the mitochondrial energy‐generating system
Authors: Janssen Antoon J. M. , Schuelke Markus , Smeitink Jan A. M. , Trijbels Frans J. M. , Sengers Rob C. A. , Lucke Barbara , Wintjes Liesbeth T. M. , Morava Eva , van Engelen Baziel G. M. , Smits Bart W. , Hol Frans A. , Siers Marloes H. , Ter Laak Henk , van der Knaap Marjo S. , Van Spronsen Francjan J. , Rodenburg Richard J. T. , van den Heuvel Lambert P.
Published: February 2008

Objective

The mitochondrial energy‐generating system (MEGS) encompasses the mitochondrial enzymatic reactions from oxidation of pyruvate to the export of adenosine triphosphate. It is investigated in intact muscle mitochondria by measuring the pyruvate oxidation and adenosine triphosphate production rates, which we refer to as the “MEGS capacity.” Currently, little is known about MEGS pathology in patients with mutations in the mitochondrial DNA. Because MEGS capacity is an indicator for the overall mitochondrial function related to energy production, we searched for a correlation between MEGS capacity and 3243A→G mutation load in muscle of patients with the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) syndrome.

Methods

In muscle tissue of 24 patients with the 3243A→G mutation, we investigated the MEGS capacity, the respiratory chain enzymatic activities, and the 3243A→G mutation load. To exclude coinciding mutations, we sequenced all 22 mitochondrial transfer RNA genes in the patients, if possible.

Results

We found highly significant differences between patients and control subjects with respect to the MEGS capacity and complex I, III, and IV activities. MEGS‐related measurements correlated considerably better with the mutation load than respiratory chain enzyme activities. We found no additional mutations in the mitochondrial transfer RNA genes of the patients.

Interpretation

The results show that MEGS capacity has a greater sensitivity than respiratory chain enzymatic activities for detection of subtle mitochondrial dysfunction. This is important in the workup of patients with rare or new mitochondrial DNA mutations, and with low mutation loads. In these cases we suggest to determine the MEGS capacity. Ann Neurol 2008
Presumed perinatal ischemic stroke: Vascular classification predicts outcomes
Authors: Kirton Adam , DeVeber Gabrielle , Pontigon Ann‐Marie , Macgregor Daune , Shroff Manohar
Published: February 2008

Objective

Perinatal stroke commonly causes childhood neurological morbidity. Presumed perinatal ischemic stroke (PPIS) defines children presenting outside a normal perinatal period with chronic, focal infarction on neuroimaging. Infarcts are assumed to represent arterial strokes, but recent evidence suggests the periventricular venous infarction (PVI) of infants born preterm may also occur in utero and present as PPIS. Using the largest published cohort, we aimed to define arterial and PVI PPIS syndromes and their outcomes.

Methods

A PPIS consecutive cohort was identified (SickKids Children's Stroke Program, 1992–2006). Systematic neuroradiological scoring executed by blinded investigators included previously defined arterial stroke syndromes. PVI criteria included unilateral injury with at least four of the following conditions: (1) focal periventricular encephalomalacia, (2) internal capsule T2 prolongation, (3) cortical and (4) relative basal ganglia sparing, and (5) remote hemorrhage. Arterial and PVI classifications were validated and correlated with neurological outcomes (Pediatric Stroke Outcome Measure).

Results

In 59 PPISs (64% male), 94% of lesions fell within potential middle cerebral artery territories. Although arterial proximal M1 infarction was most common (n = 19; 35%), venous PVI was second (n = 12; 22%) and accounted for 75% of subcortical injuries. Motor outcomes (mean follow‐up, 5.3 years) were predicted by basal ganglia involvement including leg hemiparesis, spasticity, and need for assistive devices (p < 0.01). Nonmotor outcomes were associated with cortical involvement, including cognitive/behavioral outcomes, visual deficits, and epilepsy (p < 0.01). Classification interrater reliability was excellent (correlation coefficients > 0.975).

Interpretation

Recognizable PPIS patterns predict long‐term morbidity and may guide surveillance, therapy, and counseling. PVI is an underrecognized cause of PPIS and congenital hemiplegia. Ann Neurol 2008
Material Applications for Salen Frameworks
Authors: Wezenberg Sander J. , Kleij Arjan W.
Published: February 2008

Salens are among the most widely studied ligands in chemistry. They are primarily applied in homogeneous catalysis, a use that helps to increase our knowledge of environmentally benign and cost‐attractive chemical and/or pharmaceutical processes. Lately, the interest in salen chemistry has shifted to the use of these scaffolds in various other applications in which the immense versatility of the salen framework as a molecular building block can be exploited. Herein, we highlight the most recent research involving the incorporation of salen motifs in new materials and sophisticated catalysts.
Synthesis and properties of dimethacrylates—Derivatives of maleic and fumaric acids
Authors: Matynia Tadeusz , Podgórski Maciej
Published: February 2008

In this work, the synthesis as well as the mechanical and thermal properties of dimethacrylate copolymers are investigated. These copolymers were obtained from glycidyl methacrylate, maleic and/or fumaric acid adducts, methyl methacrylate, and/or styrene. The addition reaction of glycidyl methacrylate as well as maleic and fumaric acids was carried out in the presence of basic catalyst. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Time–temperature‐transformation (TTT) diagram of the isothermal crosslinking of an epoxy/amine system: Curing kinetics and chemorheology
Authors: Mounif E. , Bellenger V. , Tcharkhtchi A.
Published: February 2008

Rotational molding is a new process for thermosets, few research works have been done on this subject. The goal of this study is to determine the optimal conditions (time, temperature, viscosity, etc) of this process for an epoxy‐amine system. The thermal and rheological analysis help us to investigate the vitrification and the gelation of the reactive system (DGEBA‐DETDA) and to draw the TTT diagram. We have completed this diagram by adding the isoviscosity curves to determine the available domain for rotational molding. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Nylon 6/organoclay nanocomposites by extrusion
Authors: González Teresa Varela , Salazar Carlos Guerrero , De la Rosa Javier Rivera , González Virgilio González
Published: February 2008

Montmorillonite‐layered silicates were modified with one tertiary alkylammonium salt (ALAS), to obtain nylon 6/montmorillonite nanocomposites. Nanocomposites were prepared by direct polymer melt‐intercalation, using two kinds of devices: twin‐screw extruder and a Brabender Plasticorder. Composites were made with different load clay to see the effect of them in the nylon composites. The modified clay was characterized by X‐ray diffraction (XRD), thermogravimetric analysis (TGA), and liquid nitrogen sorption; to evidence the intercalation of the ALAS among the layers of the montmorillonite. The nanocomposites were characterized by XRD, Fourier transform infrared spectroscopy, TGA, capillary rheometry, and mechanical tensile testing. The organoclay was well dispersed into the nylon 6 matrix when compounded with the twin‐screw extruder, but the use of a Brabender Plasticorder was less effective. The mechanical properties were modified, and the tensile modulus showed a relevant change compared with the pristine nylon 6. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Preparation of monomethyl poly(ethylene glycol)‐g‐chitosan copolymers with various degrees of substitution: Their ability to encapsulate and condense plasmid DNA
Authors: Zhang Wei , Pan Shirong , Zhang Xuan , Luo Xin , Du Zhuo
Published: February 2008

Chitosan (CS) has great potential as a nonvirus gene delivery vector, but its application is limited because of poor water solubility. Monomethyl poly(ethylene glycol) (mPEG)‐graft‐CS copolymers were synthesized by the reaction of mPEG–aldehyde (oxidized mPEG) with amino groups on CS chains; they showed enhanced solubility in water. Copolymers with various mPEG degrees of substitution (DS) and CS molecular weights were obtained, and their capabilities of DNA encapsulation were compared through gel retardation assay and particle size and ζ potential measurements. The effects of different ratios of primary amines on CS to the phosphate groups on DNA (N/P ratios), DS, and molecular weights on particle size and encapsulation efficiency were investigated. The results show that high N/P ratios and proper DS were necessary for the formation of well‐distributed complex particles. Among all of these samples, mPEG (3.55)–CS (50 kDa)/DNA complexes [where the parentheses following mPEG indicate DS (%), and the parentheses following CS indicate the molecular weight of CS] raised the ζ potential from negative to positive most quickly, yielded the smallest particle size, and were retarded in agarose gel at the lowest N/P ratio; this indicated the best efficiency of DNA encapsulation. On the contrary, mPEG (0.80)–CS (50 kDa)/DNA complexes raised the ζ potential to positive most slowly, fluctuated around the value 0 from N/P ratios of 15 : 1 to 30 : 1, and were retarded in agarose gel at the highest N/P ratio; this indicated the lowest efficiency of encapsulating plasmids. Copolymers with desirable efficiencies of DNA encapsulation could be promising gene carriers. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Effect of solvent on the chain conformation and cure behavior of phenolic resin
Authors: Yan Zhang , Yujian Liu , Qi He , Zhewen Han
Published: February 2008

The research indicates that in comparison with other solvents, such as ethanol, propanol, butyl alcohol and acetone, which are usually selected as the solvent in phenolic solution, methanol can increase curing rate and enhance crosslinking density of phenolic resins. Therefore, the chain conformations of resole dissolved in different solvents are investigated by using viscosity method. It shows that the chain conformation of resoles changes from loose coil to compact ball, as the strength of hydrogen bond between resole and solvent drops along with the decrease of polarity of solvents. The transition of the chain conformation causes the decrease of reaction probability and reaction rate between functional groups of resoles. The number of unreacted molecules increases, and the crosslinking density of cured resins decreases. The differential scanning calorimetric analysis shows that compared with the resins in methanol, ethanol, propanol, and butyl alcohol, exothermic peak of resole in acetone is obviously wider, and its peak exothermic temperature is lower. Both optical microscope pictures and atomic force microscope pictures demonstrate that the crosslinking density of resins in methanol is higher than those in other solvents. The research concludes that the type of solvent has a great influence on the curing rate and curing degree of resoles. © 2008 Wiley Periodicals, Inc. JAppl Polym Sci, 2008