Root effect hemoglobins

The Root effect describes an extreme pH sensitivity expressed in the hemoglobins of certain fish, in which it plays a unique physiological role. This review describes our general understanding of the effect of protons on the oxygen binding properties of hemoglobin and the particular properties which characterize Root effect proteins. The development of our understanding of the molecular origins of this effect is outlined and the role played by our ever expanding knowledge of protein structure is highlighted. The present state of our knowledge is detailed.     

Response to “Critical Assessment of the Evidence for Striped Nanoparticles”

Stirling et al., (10.1371/journal.pone.0108482) presented an analysis on some of our publications on the formation of stripe-like domains on mixed-ligand coated gold nanoparticles. The authors shed doubts on some of our results however no valid argument is provided against what we have shown since our first publication: scanning tunneling microscopy (STM) images of striped nanoparticles show stripe-like domains that are independent of imaging parameters and in particular of imaging speed. We have consistently ruled out the presence of artifacts by comparing sets of images acquired at different tip speeds, finding invariance of the stipe-like domains. Stirling and co-workers incorrectly analyzed this key control, using a different microscope and imaging conditions that do not compare to ours. We show here data proving that our approach is rigorous. Furthermore, we never solely relied on image analysis to draw our conclusions; we have always used the chemical nature of the particles to assess the veracity of our images. Stirling et al. do not provide any justification for the spacing of the features that we find on nanoparticles: ~1 nm for mixed ligand particles and ~ 0.5 nm for homoligand particles. Hence our two central arguments remain unmodified: independence from imaging parameters and dependence on ligand shell chemical composition. The paper report observations on our STM images; none is a sufficient condition to prove that our images are artifacts. We thoroughly addressed issues related to STM artifacts throughout our microscopy work. Stirling et al. provide guidelines for what they consider good STM images of nanoparticles, such images are indeed present in our literature. They conclude that the evidences we provided to date are insufficient, this is a departure from one of the authors’ previous article which concluded that our images were composed of artifacts. Given that four independent laboratories have reproduced our measurements and that no scientifically rigorous argument is presented to invalidate our STM images, and also given that Stirling et al. do not contest the quality of our recent STM images, we re-affirm that specific binary mixture of ligands spontaneously form features in their ligand shell that we describe as stripe-like domains ~1 nm in width.     

Autonomy reconfigured: incorporating the role of the unconscious

The principle of respect for autonomy has served as a pillar of American bioethics. Through its application in response to physician paternalism and as the basis for informed consent, it has attained preeminent status in the discipline. New challenges in health care warrant a re-examination of the origins of our autonomy. Developmental psychology, cognitive neuroscience, and behavioral neurology all emphasize the intimate relationship between our cognitive and emotional development, and through this, our conscious and unconscious minds. Our intellectual, and particularly our moral development, are instilled in us by our moral mentors, and consequently by our community as a whole. Autonomy and community are therefore inextricably interlinked, and our emphasis on liberty, rights, and privacy without the inclusion of family, community, and social responsibility is biologically unsound. Appreciation of this reality should lead to a more balanced set of bioethical norms.     

Correction: genetic algorithm learning as a robust approach to RNA editing site site prediction

After the publication of [1], we were alerted to an error in our data. The error was an one-off miscalculation in the extraction of position information for our set of true negatives. Our data set should have used randomly selected non-edited cytosines (C) as true negatives, but the data generation phase resulted in a set of nucleotides that were each one nucleotide downstream of known, unedited cytosines. The consequences of this error are reflected in changes to our results, although the general conclusions presented in our original publication remain largely unchanged.     

A radiotelemetry system for polysomnographic recordings in lambs

The use of telemetry in biomedical research is rapidly increasing and is soon likely to be standard in research fields where prolonged recordings of multiple physiologic variables are necessary in freely moving animals. We describe our experience with a radiotelemetry system designed in our laboratory for polysomnographic recordings in newborn lambs. The system comprises eight channels: four channels for electromyographic activity of respiratory muscles, and one channel each for electrocorticogram, eye movement, electrocardiogram, and nasal flow. Using this system, we report our experience on the study of respiration and spontaneous apneas in the various states of consciousness, based on more than 500 h of recordings. Addition of radiotelemetry to our armamentarium has proven to be of invaluable help for the study of neonatal apneas and has now become routine in our laboratory.     

Neurochemistry of Stress. An Overview

Stress is a word that is used very commonly. It is generally employed to design unpleasant phenomena, although it is related to a function necessary to our life. Stress in itself is not a disease. Stress is not an aggression. It is an adaptative response of our body to any demand. Nothing can be done without stress. Stress gives rise to a mobilization of our body to succeed in a group of activities necessary to individual and social life. It favors our dynamism and creativity. But this aptitude can attain its limits, when the solicitations we receive are above what we are able to perform, both in relation to our mental and physical capabilities. The brain controls the systems involved in stress. The main areas are the prefrontal cortex, the limbic system (which comprises the hippocampus and the amygdala) and the hypothalamus. Relations between the prefrontal cortex and the limbic system are important for the planification of action. The main systems of regulation are the sympathetic and parasympathetic systems, the neuro-endocrine system and last but not least the immune system. There is a relation between all our organs and the brain. The genetic aspects and the influences of our past experiences, both during childhood and in adult life, are envisaged.     

The dynamic microbiome

While our genomes are essentially static, our microbiomes are inherently dynamic. The microbial communities we harbor in our bodies change throughout our lives due to many factors, including maturation during childhood, alterations in our diets, travel, illnesses, and medical treatments. Moreover, there is mounting evidence that our microbiomes change us, by promoting health through their beneficial actions or by increasing our susceptibility to diseases through a process termed dysbiosis. Recent technological advances are enabling unprecedentedly detailed studies of the dynamics of the microbiota in animal models and human populations. This review will highlight key areas of investigation in the field, including establishment of the microbiota during early childhood, temporal variability of the microbiome in healthy adults, responses of the microbiota to intentional perturbations such as antibiotics and dietary changes, and prospective analyses linking changes in the microbiota to host disease status. Given the importance of computational methods in the field, this review will also discuss issues and pitfalls in the analysis of microbiome time-series data, and explore several promising new directions for mathematical model and algorithm development.     

The Future of Anthropology

The future of anthropology depends on what it contributes, both to thought and to society. Whether it survives, flourishes, or becomes extinct depends on anthropology's ability to become an intregal and significant, yet not subservient, part of our culture and society. To flourish, we must press outward; we must mobilize our work and ourselves to make a difference beyond the discipline and the academy. This objective implies change in our priorities and hence in our work.     

Blue genes: genetic variation in our immune genes may be a mixed blessing

Today we know that almost all aspects of disease are affected in some way by our genes. The size of the genetic contribution towards each disease shows tremendous variation, but ultimately, the key to our survival of onslaught from environmental agents lies within our gene pool.     

A craniometric study of the C. de Lange syndrome (CdLS)

After a short review of our method, we compared the results of the radiographs of 18 cases of CdLS to the results of our normal material. All of our normal statistical data was obtained from AP and lateral view radiographs at a distance of 1 m, in the prevailing conditions of everyday practice in a radiological department. We studied quantitative changes such as microcephaly and brachycephaly, and for the first time we introduced qualitative changes such as occipital rotation and the study of obliquity of the foramen magnum (line BAO). We found microcephaly in all our cases of CdLS and brachycephaly in only 72%. Furthermore, we found a lack of positive occipital rotation in all our cases of CdLS and the line BAO turned posteriorly with O higher than BA. The same conditions were observed on our normal material only in an early postnatal stage.     

Ragweed pollen sampling in Gallarate (North-West of Milan) during four years (1987–1990)

Summary Ambrosia artemisifolia (elatior), an imported pollen, never sampled in the past in the atmosphere of our country, is beconning the most important Composita responsible for late-summer pollinosis in our area.The documented increased pollen concentration confirmed greater sensitization in people coming to our allergological centre.     

The Novartis-ILAR Rheumatology Prize 2001 Osteoarthritis: from molecule to man

During our careers, we have developed new and innovative concepts pertaining to the pathophysiology of osteoarthritis which have assisted in the development of new therapeutic approaches. Moreover, our laboratory has long sought to develop protective agents for osteoarthritic structural joint tissues. The most significant concepts that have originated from our lab are briefly outlined in this commentary.     

The Novartis-ILAR Rheumatology Prize 2001 Osteoarthritis: from molecule to man

During our careers, we have developed new and innovative concepts pertaining to the pathophysiology of osteoarthritis which have assisted in the development of new therapeutic approaches. Moreover, our laboratory has long sought to develop protective agents for osteoarthritic structural joint tissues. The most significant concepts that have originated from our lab are briefly outlined in this commentary.     

Diamonds or Dragonflies? A Question of Reshaping Societal Values

I contend that our values are muddled and misplaced. As a society, Nature is grossly undervalued relative to other commodities and priorities despite its integral and central role in our psyche and culture. The increasing dissociation of humans from nature, physically, intellectually and culturally, threatens the conservation ethic and all our efforts at conserving Nature in the long term, for human benefit or for its own sake. We need to reverse the increasing human isolation from the natural environment by encouraging our children and the wider public to engage with Nature. The formative experiences thus gained might, with time, change societal priorities in favor of a renewed conservation ethic.     

Sustainable wastewater treatment: How might microbial fuel cells contribute

The need for cost-effective low-energy wastewater treatment has never been greater. Clean water for our expanding and predominantly urban global population will be expensive to deliver, eats into our diminishing carbon-based energy reserves and consequently contributes to green house gases in the atmosphere and climate change. Thus every potential cost and energy cutting measure for wastewater treatment should be explored. Microbial fuel cells (MFCs) could potentially yield such savings but, to achieve this, requires significant advances in our understanding in a few critical areas and in our designs of the overall systems. Here we review the research which might accelerate our progress towards sustainable wastewater treatment using MFCs: system control and modelling and the understanding of the ecology of the microbial communities that catalyse the generation of electricity.     

How neoteny shapes human society: Can we escape our formative years,and fight the wrong kind of populism?

This article describes aspects of our biological nature that have contributed to the dangerous current state of societal, ecological and climatological affairs. Next, it deals with stratagems to take these aspects into account, so as to allow us better choices. I will concentrate on the concepts of evolved group mechanisms and “neoteny” and explain why they direct our responses throughout our lives. The connection between our biological make-up and our vulnerability to the current rise of certain kinds of irrational, undemocratic, populism is also laid bare. I will end by listing some simple, but possibly controversial, proposals that might have value in combating these societal tendencies and help decision making in a reality-based, more scientific, manner.     

Simultaneous and selective inference: Current successes and future challenges

The previous decade can be viewed as a second golden for era Multiple Comparisons research. I argue that much of the success stems from our being able to address real current needs. At the same time, this success generated a plethora of concepts for error rate and power, as well as multiplicity of methods for addressing them. These confuse the users of our methodology and pose a threat. To avoid the threat, it is our responsibility to match our theoretical goals to the goals of the users of statistics. Only then should we match the methods to the theoretical goals. Considerations related to such needs are discussed: simultaneous inference or selective inference, testing or estimation, decision making or scientific reporting. I then further argue that the vitality of our field in the future - as a research area - depends upon our ability to continue and address the real needs of statistical analyses in current problems. Two application areas offering new challenges have received less attention in our community to date are discussed. Safety analysis in clinical trials, where I offer an aggregated safety assessment methodology and functional Magnetic Resonance Imaging.     

A systematic search method for the identification of tightly packed transmembrane parallel alpha-helices

Membrane proteins play a major role in number of biological processes such as signaling pathways. The determination of the three-dimensional structure of these proteins is increasingly important for our understanding of their structure-function relationships. Due to the difficulty in isolating membrane proteins for X-ray diffraction studies, computational techniques are being developed to generate the 3D structures of TM domains. Here, we present a systematic search method for the identification of energetically favorable and tightly packed transmembrane parallel alpha-helices. The first step in our systematic search method is the generation of 3D models for pairs of parallel helix bundles with all possible orientations followed by an energy-based filter to eliminate structures with severe non-bonded contacts. Then, a RMS-based filter was used to cluster these structures into families. Furthermore, these dimers were energy minimized using molecular mechanics force field. Finally, we identified the tightly packed parallel alpha-helices by using an interface surface area. To validate our search method, we compared our predicted GlycophorinA dimer structures with the reported NMR structures. With our search method, we are able to reproduce NMR structures of GPA with 0.9A RMSD. In addition, by considering the reported mutational data on GxxxG motif interactions, twenty percent of our predicted dimers are within in the 2.0A RMSD. The dimers obtained from our method were used to generate parallel trimeric and tetramer TM structures of GPA and found that the structure of GPA might exist only in a dimer form as reported earlier.     

论达尔文医学(Ⅱ)

一切生物功能的设计都用查理士·达尔文的自然选择理论来解释,是本文中贯彻始终的思想．探讨的中心是自然选择所挑选的适应性变化这一概念：我们与病原格斗适应性变化,病原对抗这变化而产生的适应性变化,我们为了这些变化必须付出代价而出现的不适应性,以及机体设计和现在的生活环境之间的不适应性,等等．我们希望读者将在对身体的功能以及某些异常情况的进化论解释中得到教益．     

论达尔文医学(Ⅰ)

一切生物功能的设计都用查理士．达尔文的的自然选择理论来解释,是本文中贯彻始终的思想,探讨的中心自然自动所控制所挑选的适应性变化这一概念：我们与病原格斗适应性变化,病原对抗这变而产生的知识性变化。