Physiological noise facilitates multiplexed coding of vibrotactile-like signals in somatosensory cortex.

Neurons can use different aspects of their spiking to simultaneously represent (multiplex) different features of a stimulus. For example, some pyramidal neurons in primary somatosensory cortex (S1) use the rate and timing of their spikes to, respectively, encode the intensity and frequency of vibrotactile stimuli. Doing so has several requirements. Because they fire at low rates, pyramidal neurons cannot entrain 1:1 with high-frequency (100 to 600 Hz) inputs and, instead, must skip (i.e., not respond to) some stimulus cycles. The proportion of skipped cycles must vary inversely with stimulus intensity for firing rate to encode stimulus intensity. Spikes must phase-lock to the stimulus for spike times (intervals) to encode stimulus frequency, but, in addition, skipping must occur irregularly to avoid aliasing. Using simulations and in vitro experiments in which mouse S1 pyramidal neurons were stimulated with inputs emulating those induced by vibrotactile stimuli, we show that fewer cycles are skipped as stimulus intensity increases, as required for rate coding, and that intrinsic or synaptic noise can induce irregular skipping without disrupting phase locking, as required for temporal coding. This occurs because noise can modulate the reliability without disrupting the precision of spikes evoked by small-amplitude, fast-onset signals. Specifically, in the fluctuation-driven regime associated with sparse spiking, rate and temporal coding are both paradoxically improved by the strong synaptic noise characteristic of the intact cortex. Our results demonstrate that multiplexed coding by S1 pyramidal neurons is not only feasible under in vivo conditions, but that background synaptic noise is actually beneficial.

Degeneracy in the nervous system: from neuronal excitability to neural coding.

Degeneracy is ubiquitous across biological systems where structurally different elements can yield a similar outcome. Degeneracy is of particular interest in neuroscience too. On the one hand, degeneracy confers robustness to the nervous system and facilitates evolvability: Different elements provide a backup plan for the system in response to any perturbation or disturbance. On the other, a difficulty in the treatment of some neurological disorders such as chronic pain is explained in light of different elements all of which contribute to the pathological behavior of the system. Under these circumstances, targeting a specific element is ineffective because other elements can compensate for this modulation. Understanding degeneracy in the physiological context explains its beneficial role in the robustness of neural circuits. Likewise, understanding degeneracy in the pathological context opens new avenues of discovery to find more effective therapies.

Molecular, biophysical, and pharmacological properties of calcium-activated chloride channels.

Calcium-activated chloride channels (CaCCs) are a family of anionic transmembrane ion channels. They are mainly responsible for the movement of Cl- and other anions across the biological membranes, and they are widely expressed in different tissues. Since the Cl- flow into or out of the cell plays a crucial role in hyperpolarizing or depolarizing the cells, respectively, the impact of intracellular Ca2+ concentration on these channels is attracting a lot of attentions. After summarizing the molecular, biophysical, and pharmacological properties of CaCCs, the role of CaCCs in normal cellular functions will be discussed, and I will emphasize how dysregulation of CaCCs in pathological conditions can account for different diseases. A better understanding of CaCCs and a pivotal regulatory role of Ca2+ can shed more light on the therapeutic strategies for different neurological disorders that arise from chloride dysregulation, such as asthma, cystic fibrosis, and neuropathic pain.

Nano-ophthalmology: Applications and considerations.

The advent of nanotechnology promises to drastically accelerate progress toward nanomedicine. Nanoscale particles in the size range of cellular and molecular structures, which are usually referred to as nanoparticles (NPs), can be designed to improve penetration, sustained delivery, and controlled release of different drugs for ophthalmic therapeutic applications. After explaining different forms of routinely-used NPs such as nanomicelles, nanosuspensions, liposomes, and dendrimers, potential applications of NPs for the treatment of anterior and posterior eye diseases will be discussed by highlighting their ubiquitous properties. Furthermore, genotoxicity, cytotoxicity, and neuronal toxicity, as the major limiting factors in the wider application of NPs in medical sciences have been discussed, and novel diagnostic techniques and nanomedical tools being utilized in ophthalmology have been introduced. The development of an effective, nontoxic nanoscale biomaterials, in combination with identifying the best delivery systems, will shed more light on the future applications of nanotechnology in ophthalmology.

Distribution of ABO and Rh Blood Groups in Patients With Keratoconus: A Case-Control Study.

UNLABELLED: Association of keratoconus (KC) with genetic predisposition and environmental factors has been well documented. However, no single study has investigated the possible relationship between ABO and Rh blood groups and KC. METHODS: A case-control study was designed in a university hospital enrolling 214 patients with KC in the case group and equal number of age- and sex-matched healthy subjects in the control group. Primary characteristics, ABO blood group, and Rh factors were compared between the two groups. Topographic findings of KC eyes and the severity of the diseases were investigated according to the distribution of the blood groups. RESULTS: Blood group O and Rh(+) phenotype were most frequent in both groups. There was no significant difference between the two groups in terms of ABO blood groups or Rh factors. Mean keratometery (K), central corneal thickness, thinnest corneal thickness, flat K, steep K, sphere and cylinder, spherical equivalent, and uncorrected visual acuity were all similar between ABO blood groups and Rh(+) and Rh(-) groups. However, the best spectacle-corrected visual acuity (BCVA) had the highest value in AB blood group (0.35 ± 0.22 logMAR, P=0.005). Moreover, the blood group AB revealed the highest frequency for grade 3 KC, followed by grades 1, 2, and 4 (P=0.003). CONCLUSION: We observed no significant excess of any particular blood group among KC cases compared with healthy subjects. Except BCVA, none of the keratometric or topographic findings was significantly different between blood groups.

A Comprehensive Review on Exosomes and Microvesicles as Epigenetic Factors.

Exosomes and microvesicles, which are released by most of the cells, play important roles in intracellular correspondence by transferring DNA, messenger RNA, micro RNA, and other types of RNA and proteins. Exosomes and microvesicles may contribute to the distribution of cancers and diseases through delivering the pathogenic agents to the non-infected cells; in cancers, they can modify the cells in the tumor niche and lead them to transformation. In addition, these vesicles can affect stem cell activity and their physiological properties. On the other hand, exosomes and microvesicles can be applied in the therapeutic strategies as they are small, non-viral, flexible and able to cross biological barriers. In this review, we focused on some details about the exosomes and microvesicles both functionally and structurally.

The paradoxical pro- and antiangiogenic actions of resveratrol: therapeutic applications in cancer and diabetes.

Resveratrol, a polyphenol found in grapes, peanuts, and red wine, plays different roles in diseases such as cancer and diabetes. Existing information indicates that resveratrol provides cardioprotection, as evidenced by superior postischemic ventricular recovery, reduced myocardial infarct size, and decreased number of apoptotic cardiomyocytes associated with resveratrol treatment in animal models. Cardiovascular benefits are experienced in humans with routine but not acute consumption of red wine. In this concise review, the paradoxical pro- and antiangiogenic effects of resveratrol are described, and different roles for resveratrol in the formation of new blood vessels are explained through different mechanisms. It is hypothesized that the effects of resveratrol on different cell types are not only dependent on its concentration but also on the physical and chemical conditions surrounding cells. The findings discussed herein shed light on potential therapeutic proapoptotic and antiangiogenic applications of low-dose resveratrol treatment in the prevention and treatment of different diseases.

Association between the prevalence of obstructive sleep apnoea and the severity of keratoconus.

AIM: The purpose of this study was to determine the association between prevalence of obstructive sleep apnoea (OSA) in patients with keratoconus (KC) and the severity of KC. METHODS: Six-hundred and sixteen patients with KC and 616 patients without KC in the control group were enrolled in this prospective case-control study. Both groups were matched by age, gender, and body mass index (BMI). The Berlin Questionnaire was administered in both groups. Keratometric and topographic measurements of the KC eyes were recorded. RESULTS: Seventy-six (12.3%) and 40 (6.5%) patients were identified as high risk for developing OSA in KC and control groups, respectively (p<0.001). Family history of OSA and BMI were the risk factors for OSA in the KC group, while in the control group the only risk factor for OSA was the patient's gender. Patients with KC with a high risk of OSA had a significantly higher mean K, flat K, steep K (p<0.05), and a thinner corneal thickness (p<0.05). The severity of KC decreased in both OSA groups except for the grade 4 of high risk group which was the second most frequent group after grade 1 (p=0.005). CONCLUSIONS: Our study revealed that patients with KC are at increased risk of developing OSA, and patients with KC who are at higher risk of developing OSA may have more severe KC.

Comparison of corneal measurements in keratoconic eyes using rotating Scheimpflug camera and scanning-slit topography.

AIM: To compare the anterior segment measurements obtained by rotating Scheimpflug camera (Pentacam) and Scanning-slit topography (Orbscan IIz) in keratoconic eyes. METHODS: A total of 121 patients, 71 males (58.7%) and 50 females (41.3%) (214 eyes) with the diagnosis of keratoconus (KC) were enrolled in this study. Following diagnosis of KC by slit-lamp biomicroscopic examination, central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior chamber depth (ACD), and pupil diameter (PD) were measured by a single examiner using successive instrumentation by Pentacam and Orbscan. RESULTS: There was no significant difference between the two instruments for the measurement of CCT and TCT. In contrast, scanning-slit topography measured ACD (3.46±0.40 mm vs. 3.38±0.33 mm, P=0.019) and PD (4.97±1.26 mm vs 4.08±1.19 mm, P<0.001) significantly larger than rotating Scheimpflug camera. The two devices made similar measurements for CCT (95% CI: -2.94 to 5.06, P=0.602). However, the mean difference for TCT was -6.28 (95% CI: -10.51 to -2.06, P=0.004) showing a thinner measurement by Orbscan than by Pentacam. In terms of the ACD, the mean difference was 0.08 mm (95% CI: 0.04 to 0.12, P<0.001) with Orbscan giving a slightly larger value than Pentacam. Similarly, Orbscan measurement for PD was longer than Pentacam (95% CI: 0.68 to 1.08, P<0.001). CONCLUSION: A good agreement was found between Pentacam and Orbscan concerning CCT measurement while comparing scanning-slit topography and rotating Scheimpflug camera there was an underestimation for TCT and overestimation for ACD and PD.