Concept: Orders of magnitude
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 1 year ago
Protein hydration is essential to its structure, dynamics, and function, but water-protein interactions have not been directly observed in real time at physiological temperature to our awareness. By using a tryptophan scan with femtosecond spectroscopy, we simultaneously measured the hydration water dynamics and protein side-chain motions with temperature dependence. We observed the heterogeneous hydration dynamics around the global protein surface with two types of coupled motions, collective water/side-chain reorientation in a few picoseconds and cooperative water/side-chain restructuring in tens of picoseconds. The ultrafast dynamics in hundreds of femtoseconds is from the outer-layer, bulk-type mobile water molecules in the hydration shell. We also found that the hydration water dynamics are always faster than protein side-chain relaxations but with the same energy barriers, indicating hydration shell fluctuations driving protein side-chain motions on the picosecond time scales and thus elucidating their ultimate relationship.
Electrical stimulation of the central nervous system has been widely used for decades for either fundamental research purposes or clinical treatment applications. Yet, very little is known regarding the spatial extent of an electrical stimulation. If pioneering experimental studies reported that activation threshold currents (TCs) increase with the square of the neuron-to-electrode distance over a few hundreds of microns, there is no evidence that this quadratic law remains valid for larger distances. Moreover, nowadays, numerical simulation approaches have supplanted experimental studies for estimating TCs. However, model predictions have not yet been validated directly with experiments within a common paradigm. Here, we present a direct comparison between experimental determination and modeling prediction of TCs up to distances of several millimeters. First, we combined patch-clamp recording and microelectrode array stimulation in whole embryonic mouse spinal cords to determine TCs. Experimental thresholds did not follow a quadratic law beyond 1 millimeter, but rather tended to remain constant for distances larger than 1 millimeter. We next built a combined finite element–compartment model of the same experimental paradigm to predict TCs. While theoretical TCs closely matched experimental TCs for distances <250 microns, they were highly overestimated for larger distances. This discrepancy remained even after modifications of the finite element model of the potential field, taking into account anisotropic, heterogeneous or dielectric properties of the tissue. In conclusion, these results show that quadratic evolution of TCs does not always hold for large distances between the electrode and the neuron and that classical models may underestimate volumes of tissue activated by electrical stimulation.
Whilst the fossil record of polychaete worms extends to the early Cambrian, much data on this group derive from microfossils known as scolecodonts. These are sclerotized jaw elements, which generally range from 0.1-2 mm in size, and which, in contrast to the soft-body anatomy, have good preservation potential and a continuous fossil record. Here we describe a new eunicidan polychaete, Websteroprion armstrongi gen. et sp. nov., based primarily on monospecific bedding plane assemblages from the Lower-Middle Devonian Kwataboahegan Formation of Ontario, Canada. The specimens are preserved mainly as three-dimensional moulds in the calcareous host rock, with only parts of the original sclerotized jaw walls occasionally present. This new taxon has a unique morphology and is characterized by an unexpected combination of features seen in several different Palaeozoic polychaete families. Websteroprion armstrongi was a raptorial feeder and possessed the largest jaws recorded in polychaetes from the fossil record, with maxillae reaching over one centimetre in length. Total body length of the species is estimated to have reached over one metre, which is comparable to that of extant ‘giant eunicid’ species colloquially referred to as ‘Bobbit worms’. This demonstrates that polychaete gigantism was already a phenomenon in the Palaeozoic, some 400 million years ago.
Additive manufacturing processes such as 3D printing use time-consuming, stepwise layer-by-layer approaches to object fabrication. We demonstrate the continuous generation of monolithic polymeric parts up to tens of centimeters in size with feature resolution below 100 micrometers. Continuous liquid interface production is achieved with an oxygen-permeable window below the ultraviolet image projection plane, which creates a “dead zone” (persistent liquid interface) where photopolymerization is inhibited between the window and the polymerizing part. We delineate critical control parameters and show that complex solid parts can be drawn out of the resin at rates of hundreds of millimeters per hour. These print speeds allow parts to be produced in minutes instead of hours.
Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.
Structural characteristics of the active layers in organic photovoltaic (OPV) devices play a critical role in charge generation, separation and transport. Here we report on morphology and structural control of p-DTS(FBTTh2)2:PC71BM films by means of thermal annealing and 1,8-diiodooctane (DIO) solvent additive processing, and correlate it to the device performance. By combining surface imaging with nanoscale depth-sensitive neutron reflectometry (NR) and X-ray diffraction, three-dimensional morphologies of the films are reconstituted with information extending length scales from nanometers to microns. DIO promotes the formation of a well-mixed donor-acceptor vertical phase morphology with a large population of small p-DTS(FBTTh2)2 nanocrystals arranged in an elongated domain network of the film, thereby enhancing the device performance. In contrast, films without DIO exhibit three-sublayer vertical phase morphology with phase separation in agglomerated domains. Our findings are supported by thermodynamic description based on the Flory-Huggins theory with quantitative evaluation of pairwise interaction parameters that explain the morphological changes resulting from thermal and solvent treatments. Our study reveals that vertical phase morphology of small-molecule based OPVs is significantly different from polymer-based systems. The significant enhancement of morphology and information obtained from theoretical modeling may aid in developing an optimized morphology to enhance device performance for OPVs.
- Proceedings of the National Academy of Sciences of the United States of America
- Published 9 months ago
Earth’s magnetic field, one of the most enigmatic physical phenomena of the planet, is constantly changing on various time scales, from decades to millennia and longer. The reconstruction of geomagnetic field behavior in periods predating direct observations with modern instrumentation is based on geological and archaeological materials and has the twin challenges of (i) the accuracy of ancient paleomagnetic estimates and (ii) the dating of the archaeological material. Here we address the latter by using a set of storage jar handles (fired clay) stamped by royal seals as part of the ancient administrative system in Judah (Jerusalem and its vicinity). The typology of the stamp impressions, which corresponds to changes in the political entities ruling this area, provides excellent age constraints for the firing event of these artifacts. Together with rigorous paleomagnetic experimental procedures, this study yielded an unparalleled record of the geomagnetic field intensity during the eighth to second centuries BCE. The new record constitutes a substantial advance in our knowledge of past geomagnetic field variations in the southern Levant. Although it demonstrates a relatively stable and gradually declining field during the sixth to second centuries BCE, the new record provides further support for a short interval of extreme high values during the late eighth century BCE. The rate of change during this “geomagnetic spike” [defined as virtual axial dipole moment > 160 ZAm(2) (10(21) Am(2))] is further constrained by the new data, which indicate an extremely rapid weakening of the field (losing ∼27% of its strength over ca. 30 y).
Ultralow density (< 10 mg cm-3) materials have many important technological applications, however, most of them were fabricated using either expensive materials or complicated procedures. In this study, ultralight magnetic Fe2O3/C, Co/C and Ni/C foams (with a density < 5 mg cm-3) were fabricated on centimeter-scale by pyrolyzing commercial polyurethane (PU) sponge grafted with polyelectrolyte layers based on corresponding metal acrylate at 400 oC. The ultralight foams consisted of 3D interconnected hollow tubes that have a diameter in micrometer and nanoscale wall-thickness, forming hierarchical structures from macroscopic to nanometer length scales. More interesting was that the wall-thickness and morphology of the microtubes could be tuned by controlling the concentrations of acrylic acid and metallic cation. After modification with low-surface-energy polysiloxane, the ultralight foams showed superhydrophobicity and superoleophilicity, which quickly and selectively absorbed a variety of oils from polluted water surface under magnetic field. The oil absorption capacity reached to 100 times of the foams' own weight, exhibiting one of the highest values among the existing absorptive counterparts. By controlling the composition and conformation of the grafted polyelectrolyte layers, the present approach is extendable to fabricate a variety of ultralow density materials desirable for absorptive materials, electrode materials and catalyst supports, etc.
Among various surgical treatments, lymphaticovenular anastomosis (LVA), which bypasses congested lymph into venous circulation, is the least invasive surgical treatment. However, it usually entails skin incisions of around 3 cm, and operation time of around 4 hours. With multiple supermicrosurgeons under guidance of indocyanine green lymphography, LVAs can be simultaneously performed under local anesthesia within approximately 2 hours via small skin incisions with length less than 1 cm, allowing minimally invasive lymphatic supermicrosurgery. We performed minimally invasive lymphatic supermicrosurgery on 11 limbs of compression-refractory peripheral lymphedema cases. Length of skin incision for LVA ranged from 1 to 9 mm. Average operation time was 1.82 hours. Of the11 limbs, 10 showed postoperative volume reduction. Indocyanine green lymphography clearly visualizes superficial lymph flows, which helps us to decide precise skin incision sites and find lymphatic vessels in LVA surgery, shortening skin incision length and operation time. Minimally invasive lymphatic supermicrosurgery can serve as the most reasonable treatment of compression-refractory peripheral lymphedema.
Warifteine, a bisbenzylisoquinoline alkaloid, induces relaxation by activating potassium channels in vascular myocytes.
- Clinical and experimental pharmacology & physiology
- Published about 5 years ago
This study employed functional and electrophysiological approaches to investigate the mechanisms by which warifteine, a bisbenzylisoquinoline alkaloid isolated from Cissampelos sympodialis Eichl, causes vasorelaxation in the rat thoracic aorta. Warifteine (1 pM-10 μM) induced a concentration-dependent relaxation (pD(2) =9.40±0.06, n=5) in endothelium-intact aortic rings pre-contracted with noradrenaline (10 - 100 μM). The relaxation effects were not attenuated after endothelium removal. Warifteine also induced relaxations (pD(2) =9.2±0.19,n=8) in rings pre-contracted with PGF2(alfa) (1 - 10 mM). In contrast, the relaxant activity of warifteine was nearly abolished in high-K(+) (80 mM) pre-contracted aortic rings. In preparations incubated with 20 mM KCl or K(+) channel blockers, including: TEA (1, 3 and 5 mM), iberiotoxin (20 nM), 4-aminopyridine (1 mM) or glibenclamide (10 μM), the vasorelaxant activity of warifteine was markedly reduced. Furthermore, BaCl(2) (1 mM) did not affect the relaxant effects of warifteine. In vascular myocytes, warifteine (100 nM) significantly increased whole-cell K(+) currents (at 70 mV). In nominally Ca(2+) -free conditions, warifteine did not reduce extracellular Ca(2+) -induced contractions in high-K(+) or noradrenaline (100 μM) pre-stimulated rings. 4. Taken together, these results indicate that warifteine can induce potent concentration-dependent relaxation in the rat aorta via an endothelium-independent mechanism that involves the activation of K(+) channels. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.