- Intramolecular torque, an indicator of the internal rotation direction of rotor molecules and similar systems. [Journal Article]
- PCPhys Chem Chem Phys 2016 Oct 24
- Rotation-inducing torque is ubiquitous in many molecular systems. We present a straightforward theoretical method based on forces acting on atoms and obtained from atomistic quantum mechanics calcula...
Rotation-inducing torque is ubiquitous in many molecular systems. We present a straightforward theoretical method based on forces acting on atoms and obtained from atomistic quantum mechanics calculations to quickly and qualitatively determine whether a molecule or sub-unit thereof has a tendency to rotate and, if so, around which axis and in which sense: clockwise or counterclockwise. The method also indicates which atoms, if any, are predominant in causing the rotation. Our computational approach can in general efficiently provide insights into the internal rotational degrees of freedom of all molecules and help to theoretically screen or modify them in advance of experiments or to efficiently guide a detailed analysis of their rotational behavior with more extensive computations. As an example, we demonstrate the effectiveness of the approach using a specific light-driven molecular rotary motor which was successfully synthesized and analyzed in prior experiments and simulations.
- Programmable artificial phototactic microswimmer. [Journal Article]
- NNNat Nanotechnol 2016 Oct 17
- Phototaxis is commonly observed in motile photosynthetic microorganisms. For example, green algae are capable of swimming towards a light source (positive phototaxis) to receive more energy for photo...
Phototaxis is commonly observed in motile photosynthetic microorganisms. For example, green algae are capable of swimming towards a light source (positive phototaxis) to receive more energy for photosynthesis, or away from a light source (negative phototaxis) to avoid radiation damage or to hide from predators. Recently, with the aim of applying nanoscale machinery to biomedical applications, various inorganic nanomotors based on different propulsion mechanisms have been demonstrated. The only method to control the direction of motion of these self-propelled micro/nanomotors is to incorporate a ferromagnetic material into their structure and use an external magnetic field for steering. Here, we show an artificial microswimmer that can sense and orient to the illumination direction of an external light source. Our microswimmer is a Janus nanotree containing a nanostructured photocathode and photoanode at opposite ends that release cations and anions, respectively, propelling the microswimmer by self-electrophoresis. Using chemical modifications, we can control the zeta potential of the photoanode and program the microswimmer to exhibit either positive or negative phototaxis. Finally, we show that a school of microswimmers mimics the collective phototactic behaviour of green algae in solution.
- Getting the right balance: insole design alters the static balance of people with diabetes and neuropathy. [Journal Article]
- JFJ Foot Ankle Res 2016; 9:40
- CONCLUSIONS: Insoles have an effect on static balance but not stepping reaction time. This effect is independent of neuropathy severity. The addition of a textured cover seems to counter the negative effect of an arch fill, even in participants with severe sensation loss. Static balance is unaffected by material softness or resilience. Current best practice of providing offloading insoles, with arch fill, to increase contact area and reduce peak pressure could be making people more unstable. Whilst flat, soft insoles maybe the preferable design option for those with poor balance. There is a need to develop an offloading insole that can reduce diabetic foot ulcer risk, without compromising balance.
- Venlafaxine and Oxycodone Effects on Human Spinal and Supraspinal Pain Processing: a Randomized Cross-Over Trial. [Journal Article]
- EJEur J Neurosci 2016 Oct 17
- Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids the specifi...
Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing five-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole of the foot was recorded at the tibialis anterior muscle before and after five days of treatment. For the supraspinal activity, 61-channel electroencephalogram evoked potentials (EPs) to the electrical stimulations were simultaneously recorded. Areas under curve (AUCs) of the EMG signals were analyzed. Latencies and AUCs were computed for the major EP peaks and brain source analysis was done. The NWR was decreased in venlafaxine arm (P=0.02), but the EP parameters did not change. Oxycodone increased the AUC of the EP response (P=0.04). Oxycodone also shifted the cingulate activity anteriorly in the midcingulate-operculum network (P<0.01), and the cingulate activity was increased while the operculum activity was decreased (P=0.02). Venlafaxine exerts its effects on the modulation of spinal nociceptive transmission, which may reflect changes in balance between descending inhibition and descending facilitation. Oxycodone, on the other hand, exerts its effects at the cortical level. This study sheds light on how opioids and SNRI drugs modify the human central nervous system and where their effects dominate. This article is protected by copyright. All rights reserved.
- Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels. [Review]
- TBTrends Biochem Sci 2016 Oct 12
- In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floo...
In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past 6 years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel. Here, we review these findings and discuss the many aspects of Piezo function that remain mysterious, including how Piezos convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and what molecules and mechanisms modulate Piezo function.
- At the Crossroads: The Health and Welfare of New Mothers. [Journal Article]
- CNContemp Nurse 2016 Oct 14; :1-42
- CONCLUSIONS: The related health services have been historically concerned with infant health while turning an eye to the physical recovery of the mother. There is a need for these services to be reviewed and a basis set out for universal program content that includes focus on the social and cultural context and the mother/infant connection.
- Leaf miner-induced morphological, physiological and molecular changes in mangrove plant Avicennia marina (Forsk.) Vierh. [Journal Article]
- TPTree Physiol 2016 Oct 13
- Avicennia marina (Forsk.) Vierh is a widespread mangrove species along the southeast coasts of China. Recently, the outbreak of herbivorous insect, Phyllocnistis citrella Stainton, a leaf miner, have...
Avicennia marina (Forsk.) Vierh is a widespread mangrove species along the southeast coasts of China. Recently, the outbreak of herbivorous insect, Phyllocnistis citrella Stainton, a leaf miner, have impacted on the growth of A. marina Little is reported about the responses of A. marina to leaf miner infection at the biochemical, physiological and molecular levels. Here, we reported the responses of A. marina to leaf miner infection from the aspects of leaf structure, photosynthesis, and antioxidant system and miner responsive genes expression. A. marina leaves attacked by the leaf miner exhibited significant decreases in chlorophyll, carbon and nitrogen contents, as well as a decreased photosynthetic rate. Scanning and transmission electron microscopic observations revealed that the leaf miner only invaded the upper epidermis and destroyed the epidermal cell, which lead to the exposure of salt glands. In addition, the chloroplasts of mined leaves (ML) were swollen and the thylakoids degraded. The maximal net photosynthetic rate, stomatal conductance (Gs), carboxylation efficiency (CE), dark respiration (Rd), light respiration (Rp) and quantum yields (AQE) significantly decreased in the ML, whereas the light saturation point (Lsp), light compensation point (Lcp), water loss and CO2 compensation point (Г) increased in the ML. Moreover, chlorophyll fluorescence features also had been changed by leaf miner attacks. Interestingly, higher generation rate of O2-(·) and lower antioxidant enzyme expression in the mined portion (MP) were found; on the contrary, higher H2O2 level and higher antioxidant enzyme expression in the non-mined portion (NMP) were revealed, implying that the NMP may be able to sense that the leaf miner attacks had happened in the MP of the A. marina leaf via H2O2 signaling. Besides, the protein expression of glutathione S-transferase (GST) and the glutathione (GSH) content were increased in the ML. In addition, insect resistance-related gene expression such as chitinase 3, RAR1, topless and PIF3 had significantly increased in the ML. Taken together, our data suggest that leaf miners could significantly affect leaf structure, photosynthesis, the antioxidant system and miner responsive gene expression in A. marina leaves.
- Voluntary or involuntary? A neurophysiologic approach to functional movement disorders. [Journal Article]
- HCHandb Clin Neurol 2017; 139:121-129
- Patients with functional movement disorders (FMD) experience movements as involuntary that share fundamental characteristics with voluntary actions. This apparent paradox raises questions regarding t...
Patients with functional movement disorders (FMD) experience movements as involuntary that share fundamental characteristics with voluntary actions. This apparent paradox raises questions regarding the possible sources of a subjective experience of action. In addition, it poses a yet unresolved diagnostic challenge, namely how to describe or even quantify this experience in a scientifically and clinically useful way. Here, we describe recent experimental approaches that have shed light on the phenomenology of action in FMD. We first outline the sources and content of a subjective experience of action in healthy humans and discuss how this experience may be created in the brain. Turning to FMD, we describe implicit, behavioral measures that have revealed specific abnormalities in the awareness of action in FMD. Based on these abnormalities, we propose a potential, new solution to the paradox of volition in FMD.
- Pharmaceutical development of novel lactate-based 6-fluoro-l-DOPA formulations. [Journal Article]
- EJEur J Pharm Sci 2016 Oct 4
- 6-[(18)F]fluoro-l-dihydroxyphenylalanine ((18)F-DOPA) is a diagnostic positron emission tomography (PET) agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinso...
6-[(18)F]fluoro-l-dihydroxyphenylalanine ((18)F-DOPA) is a diagnostic positron emission tomography (PET) agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinson's disease, and more recently to detect, stage and restage neuroendocrine tumors (NETs) and to search for recurrence of viable glioma tissue. The commercially available (18)F-DOPA PET radiopharmaceutical for diagnostic use in European Union countries, is formulated in an aqueous solution of acetic acid (1.05mg/mL) and has the disadvantages that, immediately before injection, the pH must be adjusted to 4.0-5.0 by the addition of a sterile solution of sodium bicarbonate (84mg/mL) causing a light and transient burning sensation at the injection site. To overcome these drawbacks, preformulation studies were accomplished to confirm that F-DOPA degradation was affected by pH. Hence, two formulations of F-DOPA, namely ND1 and ND2, were prepared maintaining the pH=5.0 using 1mM l-(+)-lactate buffer, excluding oxygen, and incorporating in the formula the chelating agent Na2EDTA (1mM). F-DOPA oxygen exposure, the presence of free metal cations in formulation and high pH values seem to promote F-DOPA degradation. The resulting formulations proved to guarantee the chemical stability of F-DOPA in solution at pH5.0, value also compatible with the direct infusion. In vitro cell viability tests on mouse skeletal muscle fibers, renal tsa201 and neuronal SH-SY5Y cell lines, and in vivo studies in rats reported elsewhere, showed cell tolerability to the new F-DOPA formulations providing the basis for their further in vivo evaluation.
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- Biosimilars in rheumatic diseases: structural and functional variability that may impact clinical and regulatory decisions. [Journal Article]
- CRClin Rheumatol 2016 Oct 6
- Biologics as therapeutic interventions for human disease represent both a distinctly modern novelty and an echo of ancient, or at least old, medical practice. The similarity lies in the sense that in...
Biologics as therapeutic interventions for human disease represent both a distinctly modern novelty and an echo of ancient, or at least old, medical practice. The similarity lies in the sense that in both the synthetic effort occurs in living organisms (an extract of a plant, animal tissue, or a cell culture) while the difference is apparent in the bioengineering required in modern methods and the corresponding flexibility to customize the therapeutic product. Although the concept of looking to living systems as a source of medically useful compounds either for research or for actual patient care has never vanished, the development of biochemistry and advances in medicinal chemistry made production by total synthesis the standard for a safe, reliable, and commercial drug production at sufficient scale. In this interval was where much of the modern apparatus for approving medical therapies came to be developed, and as such, the most proper extension of the regulatory regime to modern biologics is not entirely obvious. In particular, the notion of generics for off-patent conventional pharmaceuticals and their role in the marketplace with respect to increasing the accessibility of treatment is not congruent with the relationship between what are known as biosimilars and off-patent originating biologics. In this article, we review elements of the scientific basis for challenges in the production, use, and regulation of biosimilars. In light of these advances, we propose suggestions to modify constraints on biosimilar regulations in the interest of patient care and access to therapies.