1,663 research outputs found
Climate Change and Highland Malaria: Fresh Air for a Hot Debate
In recent decades, malaria has become established in zones at the margin of its previous distribution, especially in the highlands of East Africa. Studies in this region have sparked a heated debate over the importance of climate change in the territorial expansion of malaria, where positions range from its neglect to the reification of correlations as causes. Here, we review studies supporting and rebutting the role of climatic change as a driving force for highland invasion by malaria. We assessed the conclusions from both sides of the argument and found that evidence for the role of climate in these dynamics is robust. However, we also argue that over-emphasizing the importance of climate is misleading for setting a research agenda, even one which attempts to understand climate change impacts on emerging malaria patterns. We review alternative drivers for the emergence of this disease and highlight the problems still calling for research if the multidimensional nature of malaria is to be adequately tackled. We also contextualize highland malaria as an ongoing evolutionary process. Finally, we present Schmalhausen's law, which explains the lack of resilience in stressed systems, as a biological principle that unifies the importance of climatic and other environmental factors in driving malaria patterns across different spatio-temporal scales
Malaria parasites regulate the duration of the intra-erythrocytic cycle via serpentine receptor 10 and coordinate development with host daily rhythms
Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms
Structured Psychosocial Stress and Therapeutic Intervention: Toward a Realistic Biological Medicine
Using generalized 'language of thought' arguments appropriate to interacting cognitive modules, we explore how disease states can interact with medical treatment, including, but not limited to, drug therapy. The feedback between treatment and response creates a kind of idiotypic 'hall of mirrors' generating a pattern of 'efficacy', 'treatment failure', and 'adverse reactions' which will, from a Rate Distortion perspective, embody a distorted image of externally-imposed structured psychosocial stress. This analysis, unlike current pharmacogenetics, does not either reify 'race' or blame the victim by using genetic structure to place the locus-of-control within a group or individual. Rather, it suggests that a comparatively simple series of questions to identify longitudinal and cross-sectional stressors may provide more effective guidance for specification of individual therapy than complicated genotyping strategies of dubious meaning. These latter are likely to be both very expensive and utterly blind to the impact of structured psychosocial stress -- a euphemism for various forms of racism and ethnic cleansing -- which, we contend, is often a principal determinant of treatment outcome at both individual and community levels of organization. We propose, to effectively address 'health disparities' between populations, and in contrast to current biomedical ideology based on a simplistic genetic determinism, a richer program of biological medicine reflecting Lewontin's 'triple helix' of genes, environment, and development, a program more in concert with the realities of a basic human biology marked by hypersociality unusual in vertibrates. Aggressive social, economic, and other policies of affirmative action to redress the persisting burdens of history would be an integral component of any such project
Data reduction for spectral clustering to analyze high throughput flow cytometry data
Background: Recent biological discoveries have shown that clustering large datasets is essential for better understanding biology in many areas. Spectral clustering in particular has proven to be a powerful tool amenable for many applications. However, it cannot be directly applied to large datasets due to time and memory limitations. To address this issue, we have modified spectral clustering by adding an information preserving sampling procedure and applying a post-processing stage. We call this entire algorithm SamSPECTRAL.Results: We tested our algorithm on flow cytometry data as an example of large, multidimensional data containing potentially hundreds of thousands of data points (i.e., events in flow cytometry, typically corresponding to cells). Compared to two state of the art model-based flow cytometry clustering methods, SamSPECTRAL demonstrates significant advantages in proper identification of populations with non-elliptical shapes, low density populations close to dense ones, minor subpopulations of a major population and rare populations.Conclusions: This work is the first successful attempt to apply spectral methodology on flow cytometry data. An implementation of our algorithm as an R package is freely available through BioConductor. © 2010 Zare et al; licensee BioMed Central Ltd
NanoSERS Microfluidics platform for rapid screening for infectious diseases
Early and accurate disease detection is critical for clinical diagnosis and ultimately
determining patient outcomes. Point-of-care testing (POCT) platforms are needed in low-
resource settings and also to help the decentralisation of healthcare centres. Immunoas-
says using Surface-Enhanced Raman Spectroscopy (SERS) are especially interesting for
their increased sensitivity and specificity. Additionally, SERS can be easily translated
into POCT formats with microfluidics. In this work, a sensitive, selective, capable of
multiplexing, and reusable SERS-based biosensor was developed. The SERS immunoas-
say relies on a sandwich format, whereby a capture platform and SERS immunotags can
capture and detect a specific antigen, respectively. The SERS immunotags consisted of
gold nanostars, allowing exceptionally intense SERS signals from attached Raman re-
porters, and the covalent attachment of antibodies provided a stable antigen-antibody
binding activity. As a capture platform, a regenerated cellulose-based hydrogel provided
a robust design and the added advantage of environmental friendliness. Besides being a
transparent material with low background fluorescence and Raman signal, its high-water
retention capacity was particularly suited for preserving the high activity of covalently
bound antibodies, improving the assay time-stability. This SERS-based immunoassay was
then integrated into a microfluidic device, allowing high-throughput sample screening
allied with the high sensitivity and multiplexing features of the developed assay. The de-
vice was fabricated in less than 30 minutes by exploring direct patterning on shrinkable
polystyrene sheets for the construction of adaptable complex three-dimensional microflu-
idic chips. Finally, to validate the microfluidic system, Plasmodium falciparum infected
red blood cell culture samples were tested for malaria biomarker detection. The discrimi-
nation of SERS immunotags signals from the background was made through the direct
classical least squares method. As a result, better data fitting was achieved, compared
to the commonly used peak integral method. Considering these features, the proposed SERS-based immunoassay notably improved the detection limits of traditional enzyme-
linked immunosorbent assay approaches. Its performance was better or comparable to
existing SERS-based immunosensors. Moreover, this approach successfully overcame the
main challenges for application at POCT, including increasing reproducibility, sensitivity,
and specificity. Hence, the microfluidic SERS system represents a powerful technology
which can contribute to early diagnosis of infectious diseases, a decisive step towards
lowering their still substantial burden on health systems worldwide.A detecção precoce e precisa de doenças é fundamental para o diagnóstico clínico de-
terminando frequentemente o prognóstico do paciente. Desta forma, plataformas de teste
de rastreio (conhecidos pelo acrónimo de POCT) são extremamente necessárias, não só em
locais com poucos recursos, mas também para ajudar à descentralização dos cuidados de
saúde. Os ensaios imunológicos que utilizam a espectroscopia de Raman aumentada pela
superfície (conhecida pelo acrónimo de SERS) são particularmente interessantes pela sua
elevada sensibilidade. Além disso, os ensaios em SERS podem ser facilmente convertidos
para formatos POCT quando combinados com microfluídica. Este trabalho consistiu no
desenvolvimento de um biosensor sensível, selectivo, capaz de múltipla detecção e reuti-
lizável baseado no fenómeno de SERS. O ensaio imunológico em SERS foi realizado num
formato em sanduíche onde um antigénio específico é apreendido por uma plataforma
de captura e reconhecido por imunosondas activas em SERS. Estas sondas consistem em
nanopartículas de ouro em forma de estrela, que proporcionam um sinal de SERS intenso
proveniente das moléculas repórter de Raman ligadas às nanopartículas. As sondas ad-
quirem a especificidade necessária para o antigénio de anticorpos a elas ligados de forma
covalente, e, por conseguinte, permitem uma ligação estável antigénio-anticorpo. O hidro-
gel regenerado à base de celulose forneceu uma plataforma de captura de design robusto
e ecológico. Além de ser um material transparente com baixa fluorescência e, portanto,
de baixa interferência no sinal de Raman, é um material com uma elevada capacidade de
retenção de água tornando-o particularmente adequado para preservar a actividade dos
anticorpos ligados covalentemente. Deste modo, o hidrogel proporciona uma plataforma
de captura estável ao longo do tempo. O immunoensaio baseado em SERS desenvolvido
foi posteriormente integrado num dispositivo de microfluídica, permitindo analisar um
grande número de amostras sendo simultaneamente sensível e passível para aplicações
de análise de múltiplos antigénios. O dispositivo foi fabricado em menos de 30 minu-
tos devido à padronização directa em folhas de poliestireno contrácteis possibilitando a construção tridimensional de um dispositivo de microfluídica. Finalmente, para validar
o sistema de microfluídica, amostras de cultura de eritrócitos infectados com Plasmodium
falciparum foram testadas para detecção de biomarcadores de malária. A discriminação
dos sinais das immunosondas activas em SERS, relativamente a sinais interferentes, foi
feita através do método clássico de quadrados mínimos. Como resultado, foi conseguido
um melhor ajuste de dados em comparação com o método de cálculo do integral das
áreas das bandas habitualmente utilizado. Assim, o ensaio imunológico baseado em SERS
proposto neste trabalho permitiu obter um limite de detecção mais baixo do que o obtido
pelas abordagens tradicionais como o ensaio de imunoabsorção enzimática (conhecido
pelo acrónimo de ELISA), além de exibir um desempenho melhor ou comparável a ou-
tros sensores baseados em SERS já existentes na literatura. Adicionalmente, o sistema
desenvolvido neste trabalho permite ultrapassar desafios que impedem a utilização deste
tipo de sensores em locais de poucos recursos, apresentando valores elevados de repro-
dutibilidade, sensibilidade e especificidade. Por conseguinte, um sistema que combina
SERS e microfluídica representa uma tecnologia potencialmente importante na detecção
precoce, na esperança de que, num futuro próximo, as consequências das doenças infecci-
osas que ainda impõem um fardo substancial ao sistema de saúde a nível mundial, sejam
minoradas
STATISTICS IN THE BILLERA-HOLMES-VOGTMANN TREESPACE
This dissertation is an effort to adapt two classical non-parametric statistical techniques, kernel density estimation (KDE) and principal components analysis (PCA), to the Billera-Holmes-Vogtmann (BHV) metric space for phylogenetic trees. This adaption gives a more general framework for developing and testing various hypotheses about apparent differences or similarities between sets of phylogenetic trees than currently exists.
For example, while the majority of gene histories found in a clade of organisms are expected to be generated by a common evolutionary process, numerous other coexisting processes (e.g. horizontal gene transfers, gene duplication and subsequent neofunctionalization) will cause some genes to exhibit a history quite distinct from the histories of the majority of genes. Such “outlying” gene trees are considered to be biologically interesting and identifying these genes has become an important problem in phylogenetics.
The R sofware package kdetrees, developed in Chapter 2, contains an implementation of the kernel density estimation method. The primary theoretical difficulty involved in this adaptation concerns the normalizion of the kernel functions in the BHV metric space. This problem is addressed in Chapter 3. In both chapters, the software package is applied to both simulated and empirical datasets to demonstrate the properties of the method.
A few first theoretical steps in adaption of principal components analysis to the BHV space are presented in Chapter 4. It becomes necessary to generalize the notion of a set of perpendicular vectors in Euclidean space to the BHV metric space, but there some ambiguity about how to best proceed. We show that convex hulls are one reasonable approach to the problem. The Nye-PCA- algorithm provides a method of projecting onto arbitrary convex hulls in BHV space, providing the core of a modified PCA-type method
Data-driven modelling of biological multi-scale processes
Biological processes involve a variety of spatial and temporal scales. A
holistic understanding of many biological processes therefore requires
multi-scale models which capture the relevant properties on all these scales.
In this manuscript we review mathematical modelling approaches used to describe
the individual spatial scales and how they are integrated into holistic models.
We discuss the relation between spatial and temporal scales and the implication
of that on multi-scale modelling. Based upon this overview over
state-of-the-art modelling approaches, we formulate key challenges in
mathematical and computational modelling of biological multi-scale and
multi-physics processes. In particular, we considered the availability of
analysis tools for multi-scale models and model-based multi-scale data
integration. We provide a compact review of methods for model-based data
integration and model-based hypothesis testing. Furthermore, novel approaches
and recent trends are discussed, including computation time reduction using
reduced order and surrogate models, which contribute to the solution of
inference problems. We conclude the manuscript by providing a few ideas for the
development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and
Multiscale Dynamics (American Scientific Publishers
The Worker Honeybee Fat Body Proteome Is Extensively Remodeled Preceding a Major Life-History Transition
Honeybee workers are essentially sterile female helpers that make up the majority of individuals in a colony. Workers display a marked change in physiology when they transition from in-nest tasks to foraging. Recent technological advances have made it possible to unravel the metabolic modifications associated with this transition. Previous studies have revealed extensive remodeling of brain, thorax, and hypopharyngeal gland biochemistry. However, data on changes in the abdomen is scarce. To narrow this gap we investigated the proteomic composition of abdominal tissue in the days typically preceding the onset of foraging in honeybee workers
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