DySCo: Quantitating Associations of Membrane Proteins Using Two-Color Single-Molecule Tracking

We present a general method called dynamic single-molecule colocalization for quantitating the associations of single cell surface molecules labeled with distinct autofluorescent proteins. The chief advantages of the new quantitative approach are that, in addition to stable interactions, it is capable of measuring nonconstitutive associations, such as those induced by the cytoskeleton, and it is applicable to situations where the number of molecules is small

Mercury and selenium in developing and mature fruiting bodies of Amanita muscaria

Both mercury (Hg) and selenium (Se) occur in many mushroom species, but the morphological distribution of these elements during different developmental stages of the fruiting bodies is not known. Although Amanita muscaria can be consumed after suitable processing, they are often ignored by mushroom foragers, leaving an abundance for investigative study. Multiple specimens in each of six developmental stages (button to fully mature) were collected in excellent condition during a single morning from the same forested location and composited. With an average of 30 specimens per composite, and low temporal, spatial, and measurement uncertainty, the data are likely to be representative of the typical concentrations of Hg and Se for each developmental stage. Hg (range 0.58–0.74 mg kg-1 dry weight cap; 0.33 to 0.44 mg kg-1 dw stipe) and Se (range 8.3–11 mg kg-1dw cap; 2.2 to 4.3 mg kg-1 dw stipe) levels were observed to vary during the developmental stages, and the variability may relate to the demands in growth. In common with some other species, the lower stipe concentrations may be consistent with nutrient/content transport and support functions. Both Hg and Se levels were lowest during periods of maximum sporocarp growth. Selenium occurs at almost an order of magnitude greater levels than Hg. Due to its role in mitigating the effects of Hg toxicity, this property is of significance to those who consume the species either for nutritional, medicinal, or recreational purposes, although the losses of both these elements during processing are not know

Successful Salvage Unrelated Umbilical Cord Blood Transplantation with Two Units After Engraftment Failure with Single Unit in Severe Aplastic Anemia

Severe aplastic anemia (SAA) patients without an HLA-matched sibling donor need alternative treatment options. Umbilical cord blood transplantation (UCBT) has become an alternative means for treating various diseases, but it has not been proved to be a satisfactory method to treat SAA. Here, we report the case of a girl who underwent successful two-unit UCBT after engraftment failure with a single unit. Two-unit UCBT is proposed to have better engraftment potential and to offer a better chance of survival, according to some reports. Increased cell dose and graft-versus-graft reaction could contribute to these advantages. With this promising result, two-unit UCBT could be an alternative treatment option for patients with SAA without an HLA-matched donor

Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature

This is an accepted manuscript of an article published by Elsevier in Journal of Thermal Biology on 18/07/2017, available online: https://doi.org/10.1016/j.jtherbio.2017.07.006 The accepted version of the publication may differ from the final published version.© 2017 Elsevier Ltd The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n  =  24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants’ demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled “Thermographic Imaging in Sports and Exercise Medicine (TISEM)” which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.Published versio

The Cost of Reducing the North Atlantic Ocean Biological Carbon Pump

To predict the impacts of climate change it is essential to understand how anthropogenic change alters the balance between atmosphere, ocean, and terrestrial reservoirs of carbon. It has been estimated that natural atmospheric concentrations of CO2 are almost 200 ppm lower than they would be without the transport of organic material produced in the surface ocean to depth, an ecosystem service driven by mechanisms collectively referred to as the biological carbon pump. Here we quantify potential reductions in carbon sequestration fluxes in the North Atlantic Ocean through the biological carbon pump over the twenty-first century, using two independent biogeochemical models, driven by low and high IPCC AR5 carbon emission scenarios. The carbon flux at 1000 m (the depth at which it is assumed that carbon is sequestered) in the North Atlantic was estimated to decline between 27 and 43% by the end of the century, depending on the biogeochemical model and the emission scenario considered. In monetary terms, the value of this loss in carbon sequestration service in the North Atlantic was estimated to range between US$170–US$3000 billion in abatement (mitigation) costs and US$23–US$401 billion in social (adaptation) costs, over the twenty-first century. Our results challenge the frequent assumption that coastal habitats store more significant amounts of carbon and are under greater threat. We highlight the largely unrecognized economic importance of the natural, blue carbon sequestration service provided by the open ocean, which is predicted to undergo significant anthropogenic-driven change

Orodispersible tablets: therapeutic and technological advantages of development

Los comprimidos bucodispersables se definen como comprimidos no recubiertos destinados a ser colocados en la boca, donde se dispersan rápidamente antes de ser tragados. Estas formulaciones son conocidas por las siglas FDDT´s (Fast Dissolving Disintegrating Tablets). Son útiles para la administración a pacientes con dificultades en la deglución, presentan una elevada aceptación por parte del paciente, mejoran de la biodisponibilidad del principio activo y suponen una nueva alternativa para la industria farmacéutica. Dentro de sus inconvenientes destacan el poco conocimiento por parte del paciente, la baja resistencia mecánica, su mayor susceptibilidad a la degradación por temperatura y humedad; la falta, a veces, de bioequivalencia con las formulaciones convencionales, y la dificultad de obtener liberaciones prolongadas o retardadas del principio activo.A nivel tecnológico, existen varios procesos que se pueden aplicar en su elaboración. Con los métodos clásicos de elaboración de comprimidos, mediante la correcta selección de los excipientes y de las variables de la etapa de compresión se obtienen unos comprimidos en los que existe un equilibrio entre dureza y disgregación. Han surgido una serie de tecnologías novedosas: Flashtab, Wowtab, Orasolv y Durasolv. Otra opción es el empleo de técnicas de liofilización, aunque presenta como desventaja su alto coste. Algunas tecnologías especiales patentadas como son Lyoc, QuickSolv y Zydis. Por último, estos comprimidos se pueden elaborar por el método de los polímeros entrecruzados, también conocido como FlashDose y se basa en la formación de una matriz de hilos de azúcares entrelazados.The orally disintegrating tablets are defined as non-coated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed. These formulations are known by the acronym FDDT's (Fast Dissolving Disintegrating Tablets). They are useful for administration to patients with swallowing difficulties, have a high acceptance by the patient, improve bioavailability of the active ingredient and represent a new alternative for the pharmaceutical industry. Among its disadvantages include limited knowledge by the patient, low mechanical strength, increased susceptibility to degradation by temperature and humidity; lack sometimes bioequivalence with conventional formulations, and the difficulty of obtaining prolonged release or delayed active ingredient. At the technological level, there are several processes that can be applied in their preparation. With classical methods of tabletting, by proper selection of excipients and the variables of the compression stage a tablet in which there is a balance between hardness and disintegration are obtained. Flashtab, Wowtab, Orasolv and Durasolv: They have a number of new technologies emerged. Another option is the use of freeze drying techniques, but has the disadvantage of its high cost. Some special patented technologies such as Lyoc, QuickSolv and Zydis. Finally, these tablets may be made by the method of Crosslinked polymers, also known as FlashDose and is based on the formation of a matrix of interwoven threads sugars

Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice

The mouse mutant mnd2 (motor neuron degeneration 2) exhibits muscle wasting, neurodegeneration, involution of the spleen and thymus, and death by 40 days of age(1,2). Degeneration of striatal neurons, with astrogliosis and microglia activation, begins at around 3 weeks of age, and other neurons are affected at later stages'. Here we have identified the mnd2 mutation as the missense mutation Ser276Cys in the protease domain of the nuclear-encoded mitochondrial serine protease Omi (also known as HtrA2 or Prss25). Protease activity of Omi is greatly reduced in tissues of mnd2 mice but is restored in mice rescued by a bacterial artificial chromosome transgene containing the wildtype Omi gene. Deletion of the PDZ domain partially restores protease activity to the inactive recombinant Omi protein carrying the Ser276Cys mutation, suggesting that the mutation impairs substrate access or binding to the active site pocket. Loss of Omi protease activity increases the susceptibility of mitochondria to induction of the permeability transition, and increases the sensitivity of mouse embryonic fibroblasts to stress-induced cell death. The neurodegeneration and juvenile lethality in mnd2 mice result from this defect in mitochondrial Omi protease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62561/1/nature02052.pd

Activities of Rifampin, Rifapentine and Clarithromycin Alone and in Combination against Mycobacterium ulcerans Disease in Mice

Buruli ulcer (BU) is found throughout the world but is particularly prevalent in West Africa. Until 2004, treatment for this disfiguring disease was surgical excision followed by skin grafting, procedures often requiring months of hospitalization. More recently, an 8-week regimen of oral rifampin and streptomycin administered by injection has become the standard of care recommended by the World Health Organization. However, daily injections require sterile needles and syringes to prevent spread of blood borne pathogens and streptomycin has potentially serious side effects, most notably hearing loss. We tested an entirely oral regimen, substituting the long acting rifapentine for rifampin and clarithromycin for streptomycin. We also evaluated each drug separately. We found that rifapentine alone is as good as rifampin plus streptomycin, but the simultaneous addition of effective clarithromycin doses, at least in the mouse, reduces the activity of both rifampin and rifapentine, making it difficult to assess the efficacy of the oral regimens in the model. Studies of serum drug concentrations indicated that separating treatment times by one hour or reducing the clarithromycin dose to one active in humans should overcome this issue in experimental and clinical BU treatment, respectively

The Red Sea, Coastal Landscapes, and Hominin Dispersals

This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization