For the first time in modern scientific history, chikungunya virus has established its mosquito-human transmission cycle in the Americas. The history of dengue control, recent findings on chikungunya ...strain variation, and public health preparedness indicate the likelihood of the further spread of this outbreak.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The predominantly deep-sea hexactinellid sponges are known for their ability to construct remarkably complex skeletons from amorphous hydrated silica. The skeletal system of one such species of ...sponge, Euplectella aspergillum, consists of a square-grid-like architecture overlaid with a double set of diagonal bracings, creating a chequerboard-like pattern of open and closed cells. Here, using a combination of finite element simulations and mechanical tests on 3D-printed specimens of different lattice geometries, we show that the sponge's diagonal reinforcement strategy achieves the highest buckling resistance for a given amount of material. Furthermore, using an evolutionary optimization algorithm, we show that our sponge-inspired lattice geometry approaches the optimum material distribution for the design space considered. Our results demonstrate that lessons learned from the study of sponge skeletal systems can be exploited for the realization of square lattice geometries that are geometrically optimized to avoid global structural buckling, with implications for improved material use in modern infrastructural applications.
The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of ...arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chikungunya fever (CHIKF) is an emerging infectious disease caused by an alphavirus transmitted by Aedes spp. mosquitoes. Because mosquito control programs are not highly efficient for outbreak ...containment, vaccines are essential to reduce the burden of disease. Although no licensed vaccine against CHIKF is yet available, many highly promising candidates are undergoing preclinical studies, and a few of them have been tested in human trials of phase 1 or 2. Here, we review recent findings regarding the need for a CHIKF vaccine and provide an update on vaccines nearing or having entered clinical trials. We also address needs to tackle bottlenecks to vaccine development-including scientific and financial barriers-and to accelerate the development of vaccines; several actions should be taken: (i) design efficacy trials to be conducted during the course of outbreaks; (ii) evaluate the opportunity for adopting the "animal rule"for demonstration of efficacy for regulatory purposes; (iii) strengthen the collective commitment of nations, international organizations, potential donors and industry; (iv) stimulate public and/or private partnerships to invest in vaccine development and licensure; and (v) identify potential markets for an effective and safe CHIKF vaccine.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lifestyle choices influence 20–40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing ...risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table
1
). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al.
1
published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation
1
.
Lifestyle Factor
Grade
Macronutrients
Fat
D
Protein
C
Micronutrients
Calcium
A
Vitamin D
B
Micronutrients other than calcium and vitamin D
D
Food Patterns
Dairy
B
Fiber
C
Fruits and vegetables
C
Detriment of cola and caffeinated beverages
C
Infant Nutrition
Duration of breastfeeding
D
Breastfeeding versus formula feeding
D
Enriched formula feeding
D
Adolescent Special Issues
Detriment of oral contraceptives
D
Detriment of DMPA injections
B
Detriment of alcohol
D
Detriment of smoking
C
Physical Activity and Exercise
Effect on bone mass and density
A
Effect on bone structural outcomes
B
Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years—a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one’s genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.
Advances in fabrication technologies are enabling the production of architected materials with unprecedented properties. Most such materials are characterized by a fixed geometry, but in the design ...of some materials it is possible to incorporate internal mechanisms capable of reconfiguring their spatial architecture, and in this way to enable tunable functionality. Inspired by the structural diversity and foldability of the prismatic geometries that can be constructed using the snapology origami technique, here we introduce a robust design strategy based on space-filling tessellations of polyhedra to create three-dimensional reconfigurable materials comprising a periodic assembly of rigid plates and elastic hinges. Guided by numerical analysis and physical prototypes, we systematically explore the mobility of the designed structures and identify a wide range of qualitatively different deformations and internal rearrangements. Given that the underlying principles are scale-independent, our strategy can be applied to the design of the next generation of reconfigurable structures and materials, ranging from metre-scale transformable architectures to nanometre-scale tunable photonic systems.
Although the functional properties of shark skin have been of considerable interest to both biologists and engineers because of the complex hydrodynamic effects of surface roughness, no study to date ...has successfully fabricated a flexible biomimetic shark skin that allows detailed study of hydrodynamic function. We present the first study of the design, fabrication and hydrodynamic testing of a synthetic, flexible, shark skin membrane. A three-dimensional (3D) model of shark skin denticles was constructed using micro-CT imaging of the skin of the shortfin mako (Isurus oxyrinchus). Using 3D printing, thousands of rigid synthetic shark denticles were placed on flexible membranes in a controlled, linear-arrayed pattern. This flexible 3D printed shark skin model was then tested in water using a robotic flapping device that allowed us to either hold the models in a stationary position or move them dynamically at their self-propelled swimming speed. Compared with a smooth control model without denticles, the 3D printed shark skin showed increased swimming speed with reduced energy consumption under certain motion programs. For example, at a heave frequency of 1.5 Hz and an amplitude of ± 1 cm, swimming speed increased by 6.6% and the energy cost-of-transport was reduced by 5.9%. In addition, a leading-edge vortex with greater vorticity than the smooth control was generated by the 3D printed shark skin, which may explain the increased swimming speeds. The ability to fabricate synthetic biomimetic shark skin opens up a wide array of possible manipulations of surface roughness parameters, and the ability to examine the hydrodynamic consequences of diverse skin denticle shapes present in different shark species.
Analysis of enterovirus infection is difficult in animals because they express different virus receptors than humans, and static cell culture systems do not reproduce the physical complexity of the ...human intestinal epithelium. Here, using coxsackievirus B1 (CVB1) as a prototype enterovirus strain, we demonstrate that human enterovirus infection, replication and infectious virus production can be analyzed in vitro in a human Gut-on-a-Chip microfluidic device that supports culture of highly differentiated human villus intestinal epithelium under conditions of fluid flow and peristalsis-like motions. When CVB1 was introduced into the epithelium-lined intestinal lumen of the device, virions entered the epithelium, replicated inside the cells producing detectable cytopathic effects (CPEs), and both infectious virions and inflammatory cytokines were released in a polarized manner from the cell apex, as they could be detected in the effluent from the epithelial microchannel. When the virus was introduced via a basal route of infection (by inoculating virus into fluid flowing through a parallel lower 'vascular' channel separated from the epithelial channel by a porous membrane), significantly lower viral titers, decreased CPEs, and delayed caspase-3 activation were observed; however, cytokines continued to be secreted apically. The presence of continuous fluid flow through the epithelial lumen also resulted in production of a gradient of CPEs consistent with the flow direction. Thus, the human Gut-on-a-Chip may provide a suitable in vitro model for enteric virus infection and for investigating mechanisms of enterovirus pathogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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