Theoretical analysis of cargo transport by catch bonded motors in optical trapping assays.

Dynein motors exhibit catch bonding, where the unbinding rate of the motors from microtubule filaments decreases with increasing opposing load. The implications of this catch bond on the transport properties of dynein-driven cargo are yet to be fully understood. In this context, optical trapping assays constitute an important means of accurately measuring the forces generated by molecular motor proteins. We investigate, using theory and stochastic simulations, the transport properties of cargo transported by catch bonded dynein molecular motors - both singly and in teams - in a harmonic potential, which mimics the variable force experienced by cargo in an optical trap. We estimate the biologically relevant measures of first passage time - the time during which the cargo remains bound to the microtubule and detachment force - the force at which the cargo unbinds from the microtubule, using both two-dimensional and one-dimensional force balance frameworks. Our results suggest that even for cargo transported by a single motor, catch bonding may play a role depending on the force scale which marks the onset of the catch bond. By comparing with experimental measurements on single dynein-driven transport, we estimate realistic bounds of this catch bond force scale. Generically, catch bonding results in increased persistent motion, and can also generate non-monotonic behaviour of first passage times. For cargo transported by multiple motors, emergent collective effects due to catch bonding can result in non-trivial re-entrant phenomena wherein average first passage times and detachment forces exhibit non-monotonic behaviour as a function of the stall force and the motor velocity.

Ponticulus Posticus: An Important Diagnostic Finding Often Missed in Lateral Cephalograms.

AIM: The purpose of the current study was to investigate the presence of the ponticulus posticus (PP) frequently encountered in lateral cephalograms. MATERIALS AND METHODS: About 500 patients of age 12-40 years were selected whose digital lateral cephalogram was recorded and traced to confirm the presence of the PP and categorize as: (A) Absent, as evidenced by lateral cephalograms. (B) Complete PP evidenced by the presence of circumferential bone bridge that connected the upper articular process to the atlas's posterior arch. (C) Partial PP: presented as a bone spike that protruded from the top articular process or the posterior arch of the atlas and extended above the vertebral artery sulcus. Symptoms of migraine, shoulder discomfort, orofacial pain, and headache were also evaluated on interaction with the patients. Using the Chi-square test, the relationship between the patient's gender and the presence of the PP was assessed. A p-value of 0.05 or less was regarded as statistically significant. RESULTS: About 10% of the patients reported with the presence of complete variant, 70% with partial variant and rest 20% of patients with neither a partial nor a complete form of PP. There was no statistically significant association between the PP and gender, as indicated by the Chi-square values (3.146; p = 0.526). CONCLUSION: On conclusion, according to the findings of the current study, patients with a complete form of PP experience more symptoms than those with a partial form of PP. In both groups, the PP frequency was higher in females. CLINICAL SIGNIFICANCE: In lateral cephalograms, the cervical spine region is typically ignored and given little weight. A common variation of atlas vertebrae is the PP, which is located in the posterior arch of the atlas. The PP exacerbates symptoms, such as migraine, tension headaches, shoulder pain, double vision, vertigo, stroke, and pain in the neck and orofacial region. Therefore, orthodontic specialists serve as initial diagnosticians and direct the patients to qualified physicians so that they can experience symptom relief.

Anomalous diffusion of E. coli under microfluidic confinement and chemical gradient.

We report a two-layer microfluidic device to study the combined effect of confinement and chemical gradient on the motility of wild-type E. coli. We track individual E. coli in 50 µm and 10 µm wide microchannels, with a channel height of 2 µm, to generate quasi-2D conditions. We find that contrary to expectations, bacterial trajectories are superdiffusive even in the absence of a chemical (glucose) gradient. The superdiffusive behaviour becomes more pronounced upon introducing a chemical gradient or strengthening the lateral confinement. Run length distributions for weak lateral confinement in the absence of chemical gradients follow an exponential distribution. Both confinement and chemoattraction induce deviations from this behaviour, with the run length distributions approaching a power-law form under these conditions. Both confinement and chemoattraction suppress large-angle tumbles as well. Our results suggest that wild-type E. coli modulates both its runs and tumbles in a similar manner under physical confinement and chemical gradient. Our findings have implications for understanding how bacteria modulate their motility behaviour in natural habitats.

Prevalence of Ectopic Canine in Different Sagittal and Vertical Skeletal Patterns.

AIM: The present investigation aims to find out the prevalence of ectopic canines among skeletal class I, II, and III malocclusions and to evaluate its variability among different genders and their growth patterns. MATERIAL AND METHODS: The study sample included orthopantomograms (OPGs), lateral skull views, and study models of 999 patients collected from departmental archives. Among the selected samples, 258 were males and 738 were females. They were divided into skeletal class I, II, and III malocclusions sagittally and hypodivergent, normodivergent, and hyperdivergent groups according to their angle formed between point A-Nasion - point B (ANB) and angle formed between the Sella-Nasion (SN) plane and Gonion (Go) - Gnathion (Gn) plane (SnGoGn) values respectively. RESULTS: Of the 999 samples, 738 (73.9%) were female and 260 (25.8%) were male patients. When compared to men, females had a higher proportion of ectopic canines. An estimated 62.3% of skeletal class I, 29.1% of skeletal class II, and 8.6% of skeletal class III cases were found to have ectopic canines. An estimated 720 (72.1%) patients were found to have maxillary ectopic canines and out of the available sample, 474 patients have horizontal growth patterns, 335 have average growth patterns and 190 patients have vertical growth patterns. Labial impaction was the commonest (65.4%) followed by palatal (24.8%). Bilateral impaction was comparatively more (51.1%) than unilateral impaction (48.2%). Maxilla was more prevalent (72.1%) as compared to the mandible (16.3%) and for both the arches it was (11.6%). Ectopic canines were identified in a total of 62.3% of cases with skeletal class I, 29.1% of cases with skeletal class II, and 8.6% of cases with skeletal class III. CONCLUSION: The bilateral ectopic canine was mostly seen in skeletal class I and class III malocclusions, whereas, a unilateral presentation was mostly seen in skeletal class II malocclusions. CLINICAL SIGNIFICANCE: Knowing the likelihood of a maxillary canine erupting ectopically will aid clinicians in starting with interceptive therapy since this condition necessitates complex orthodontic mechanics.

Ultrafast time-resolved carrier dynamics in tellurium nanowires using optical pump terahertz probe spectroscopy.

We report carrier relaxation dynamics in semiconducting tellurium nanowires (average diameter ∼ 10 nm) using ultrafast time-resolved terahertz spectroscopy. After photoexcitation using an 800 nm pump pulse, we observed an initial increase in the THz conductivity due to the absorption of THz radiation by photoexcited carriers. The time evolution of the differential conductivity (Δσ(τpp) = σpump on(τpp) - σpump off) shows a bi-exponential relaxation with the initial fast decay time scale of τ1 ∼ 25 ps followed by a longer relaxation time constant of τ2 ∼ 100 ps. Interestingly, the two time scales depend on the amount of the capping agent present on the surface of TeNWs, showing a faster relaxation of the photoexcited carriers as the percentage of capping decreases. This is physically interpreted as the surface state mediated relaxation mechanism of the photo-pumped carriers depending on the density of available surface states. A quantitative understanding is obtained using a coupled rate equation model taking into account the decay mechanisms determined from the surface mediated relaxation rate (DS) and direct recombination rate (DR) of the electron-hole pairs. Furthermore, the measured lattice temperature (TL) dependent dynamics, showing a faster relaxation at lower temperature, is understood using the same rate equation model, giving a power law dependence of the electron-hole recombination rate (DR) on TL as DR ∝ TL-1/2. This is explained by estimating DR using the van Roosbroeck-Shockley theory taking into account the density of states () of one-dimensional nanowires. Furthermore, to understand the measured frequency-dependent THz photoconductivity, we model Δσ(ω) using the Boltzmann transport equation taking into account the energy-dependent scattering rates showing the dominant role of short range (Γsr) and Coulomb scattering (ΓC) rates in the relaxation process, which further provides a measure of the charged and neutral impurity concentrations.

Predicting scale-dependent chromatin polymer properties from systematic coarse-graining.

Simulating chromatin is crucial for predicting genome organization and dynamics. Although coarse-grained bead-spring polymer models are commonly used to describe chromatin, the relevant bead dimensions, elastic properties, and the nature of inter-bead potentials are unknown. Using nucleosome-resolution contact probability (Micro-C) data, we systematically coarse-grain chromatin and predict quantities essential for polymer representation of chromatin. We compute size distributions of chromatin beads for different coarse-graining scales, quantify fluctuations and distributions of bond lengths between neighboring regions, and derive effective spring constant values. Unlike the prevalent notion, our findings argue that coarse-grained chromatin beads must be considered as soft particles that can overlap, and we derive an effective inter-bead soft potential and quantify an overlap parameter. We also compute angle distributions giving insights into intrinsic folding and local bendability of chromatin. While the nucleosome-linker DNA bond angle naturally emerges from our work, we show two populations of local structural states. The bead sizes, bond lengths, and bond angles show different mean behavior at Topologically Associating Domain (TAD) boundaries and TAD interiors. We integrate our findings into a coarse-grained polymer model and provide quantitative estimates of all model parameters, which can serve as a foundational basis for all future coarse-grained chromatin simulations.

Dynamic modelling predicts lactate and IL-1ß as interventional targets in metabolic-inflammation-clock regulatory loop in glioma.

In an attempt to understand the role of dysregulated circadian rhythm in glioma, our recent findings highlighted the existence of a feed-forward loop between tumour metabolite lactate, pro-inflammatory cytokine IL-1ß and circadian CLOCK. To further elucidate the implication of this complex interplay, we developed a mathematical model that quantitatively describes this lactate dehydrogenase A (LDHA)-IL-1ß-CLOCK/BMAL1 circuit and predicts potential therapeutic targets. The model was calibrated on quantitative western blotting data in two glioma cell lines in response to either lactate inhibition or IL-1ß stimulation. The calibrated model described the experimental data well and most of the parameters were identifiable, thus the model was predictive. Sensitivity analysis identified IL-1ß and LDHA as potential intervention points. Mathematical models described here can be useful to understand the complex interrelationship between metabolism, inflammation and circadian rhythm, and in designing effective therapeutic strategies. Our findings underscore the importance of including the circadian clock when developing pharmacological approaches that target aberrant tumour metabolism and inflammation. Insight box  The complex interplay of metabolism-inflammation-circadian rhythm in tumours is not well understood. Our recent findings provided evidence of a feed-forward loop between tumour metabolite lactate, pro-inflammatory cytokine IL-1ß and circadian CLOCK/BMAL1 in glioma. To elucidate the implication of this complex interplay, we developed a mathematical model that quantitatively describes this LDHA-IL-1ß-CLOCK/BMAL1 circuit and integrates experimental data to predict potential therapeutic targets. The study employed a multi-start optimization strategy and profile likelihood estimations for parameter estimation and assessing identifiability. The simulations are in reasonable agreement with the experimental data. Sensitivity analysis found LDHA and IL-1ß as potential therapeutic points. Mathematical models described here can provide insights to understand the complex interrelationship between metabolism, inflammation and circadian rhythm, and in identifying effective therapeutic targets.

Connecting the Dots: The Interplay Between Stroke and the Gut-Brain Axis.

This article discusses the interplay between the gut-brain axis and stroke, a multifaceted neurological disorder that affects millions of people worldwide. The gut-brain axis is a bidirectional communication network linking the central nervous system (CNS) to the gastrointestinal tract (GIT), including the enteric nervous system (ENS), vagus nerve, and gut microbiota. Dysbiosis in the gut microbiota, alterations in the ENS and vagus nerve, and gut motility changes have been linked to increased inflammation and oxidative stress, which are contributing factors in the development and progression of stroke. Research on animals has shown that modifying the gut microbiota can impact the results of a stroke. Germ-free mice displayed improved neurological function and decreased infarct volumes, indicating a positive effect. Furthermore, studies in stroke patients have shown alterations in the gut microbiota composition, indicating that targeting dysbiosis could be a potential therapeutic strategy for stroke. The review suggests that targeting the gut-brain axis may represent a potential therapeutic approach to reduce the morbidity and mortality associated with stroke.

Exploring the Correlation Between Influenza A Virus (H3N2) Infections and Neurological Manifestations: A Scoping Review.

Influenza A virus (IAV), particularly the H3N2 variant, is known to cause respiratory manifestations, but it can also lead to neurological complications ranging from mild symptoms like headache and dizziness to severe conditions such as encephalitis and acute necrotizing encephalopathy (ANE). In this article, the correlation between the H3N2 variant of the IAV and neurological manifestations is discussed. Additionally, prompt recognition and treatment of influenza-associated neurological manifestations are highlighted to prevent infection-related long-term complications. This review briefly discusses various neurological complications linked to IAV infections, such as encephalitis, febrile convulsions, and acute disseminated encephalomyelitis, and the potential mechanisms involved in the development of neurological complications.

Multivalent binding proteins can drive collapse and reswelling of chromatin in confinement.

Collapsed conformations of chromatin have been long suspected of being mediated by interactions with multivalent binding proteins, which can bring together distant sections of the chromatin fiber. In this study, we use Langevin dynamics simulation of a coarse grained chromatin polymer to show that the role of binding proteins can be more nuanced than previously suspected. In particular, for chromatin polymer in confinement, entropic forces can drive reswelling of collapsed chromatin with increasing binder concentrations, and this reswelling transition happens at physiologically relevant binder concentrations. Both the extent of collapse, and also of reswelling depends on the strength of confinement. We also study the kinetics of collapse and reswelling and show that both processes occur in similar timescales. We characterise this reswelling of chromatin in biologically relevant regimes and discuss the non-trivial role of multivalent binding proteins in mediating the spatial organisation of the genome.

The "3D Versascrew": An Innovative Approach for Management of Bilateral Cleft Lip and Palate Case.

The purpose behind the innovation of modified nasoalveolar moulding appliance was to achieve simultaneous anteroposterior and transverse correction in bilateral cleft cases with minimal vomeroid bending. This paper presents a 3D Versascrew appliance that has been used for presurgical nasoalveolar moulding in a 15-day-old neonate with bilateral cleft. Treatment was initiated at 30 days and continued for 90 days following which mild expansion of posterior maxilla with establishment of arch continuity and concomitant improvement in nasal morphology was achieved towards the end.

Pseudocleavage furrows restrict plasma membrane-associated PH domain in syncytial Drosophila embryos.

Syncytial cells contain multiple nuclei and have local distribution and function of cellular components despite being synthesized in a common cytoplasm. The syncytial Drosophila blastoderm embryo shows reduced spread of organelle and plasma membrane-associated proteins between adjacent nucleo-cytoplasmic domains. Anchoring to the cytoarchitecture within a nucleo-cytoplasmic domain is likely to decrease the spread of molecules; however, its role in restricting this spread has not been assessed. In order to analyze the cellular mechanisms that regulate the rate of spread of plasma membrane-associated molecules in the syncytial Drosophila embryos, we express a pleckstrin homology (PH) domain in a localized manner at the anterior of the embryo by tagging it with the bicoid mRNA localization signal. Anteriorly expressed PH domain forms an exponential gradient in the anteroposterior axis with a longer length scale compared with Bicoid. Using a combination of experiments and theoretical modeling, we find that the characteristic distribution and length scale emerge due to plasma membrane sequestration and restriction within an energid. Loss of plasma membrane remodeling to form pseudocleavage furrows shows an enhanced spread of PH domain but not Bicoid. Modeling analysis suggests that the enhanced spread of the PH domain occurs due to the increased spread of the cytoplasmic population of the PH domain in pseudocleavage furrow mutants. Our analysis of cytoarchitecture interaction in regulating plasma membrane protein distribution and constraining its spread has implications on the mechanisms of spread of various molecules, such as morphogens in syncytial cells.

Novel mechanism for oscillations in catchbonded motor-filament complexes.

Generation of mechanical oscillations is ubiquitous to a wide variety of intracellular processes, ranging from activity of muscle fibers to oscillations of the mitotic spindle. The activity of motors plays a vital role in maintaining the integrity of the mitotic spindle structure and generating spontaneous oscillations. Although the structural features and properties of the individual motors are well characterized, their implications on the functional behavior of motor-filament complexes are more involved. We show that force-induced allosteric deformations in dynein, which result in catchbonding behavior, provide a generic mechanism to generate spontaneous oscillations in motor-cytoskeletal filament complexes. The resultant phase diagram of such motor-filament systems-characterized by force-induced allosteric deformations-exhibits bistability and sustained limit-cycle oscillations in biologically relevant regimes, such as for catchbonded dynein. The results reported here elucidate the central role of this mechanism in fashioning a distinctive stability behavior and oscillations in motor-filament complexes such as mitotic spindles.

Effectiveness on knowledge about computer vision syndrome among medical coding trainee in medical coding training institute in urban Chennai, Tamil Nadu - A cross- sectional study.

CONTEXT: Electronic devices, laptops, tablets, ipad and smart phones are an integral part of one's life both in work and personal space. Excessive usage of these devices had led to health-related problems of which computer vision syndrome (CVS) is at risk of becoming a major public health issue. AIMS: Our study aimed to assess the pre-test and post-test level of knowledge regarding CVS among the medical coding trainees and also to determine the effectiveness (Video Teaching Programme) of knowledge about the CVS among them. METHODS AND MATERIAL: After obtaining ethical committee clearance using universal sampling method 480 medical coding trainees working in a firm was included in this study. A structured questionnaire was used to interview and a video teaching programme was given between the pre and post-test sessions for about 45 minutes regarding the effects of Computer Vision Syndrome. RESULTS: The level of knowledge about CVS among medical coding trainees in the pre-test and post-test was 280 (58.3%) and 8 (1.7%) had inadequate knowledge, respectively. With regards to adequate level of knowledge 24 (3%) and 328 (68.3%) had in pre-test and post-test phase, respectively. The comparison of knowledge shows a very good improvement among the medical coding trainees which was significant (p < 0.001). CONCLUSIONS: The study highlights health education as an important factor in increasing the knowledge. From a primary care point of view, knowledge regarding CVS helps in differentiating and addressing the ocular symptoms, headache and shoulder pain symptoms of other aetiology if history is elicited properly.

Dirac surface plasmons in photoexcited bismuth telluride nanowires: optical pump-terahertz probe spectroscopy.

Collective excitation of Dirac plasmons in graphene and topological insulators has opened new possibilities of tunable plasmonic materials ranging from THz to mid-infrared regions. Using time resolved Optical Pump-Terahertz Probe (OPTP) spectroscopy, we demonstrate the presence of plasmonic oscillations in bismuth telluride nanowires (Bi2Te3 NWs) after photoexcitation using an 800 nm pump pulse. In the frequency domain, the differential conductivity (Δσ = σpump on-σpump off) spectrum shows a Lorentzian response where the resonance frequency (ωp), attributed to surface plasmon oscillations, shifts with photogenerated carrier density (n) as . This dependence establishes the absorption of THz radiation by the Dirac surface plasmon oscillations of the charge carriers in the Topological Surface States (TSS) of Bi2Te3 NWs. Moreover, we obtain a modulation depth, tunable by pump fluence, of ∼40% over the spectral range of 0.5 to 2.5 THz. In addition, the time evolution of Δσ(t) represents a long relaxation channel lasting for more than 50 ps. We model the decay dynamics of Δσ(t) using coupled second order rate equations, highlighting the contributions from surface recombination as well as from trap mediated relaxation channels of the photoinjected carriers.

The Role of Salivary Lactate Levels in assessing the Severity of Septic Shock.

Background: Sepsis is a major worldwide cause of morbidity and mortality. Hence, rapid and reliable diagnosis is essential. Emergency departments use a standard measure of sepsis, based upon an elevated Lactate level in blood. Saliva is more readily available and easier to obtain than blood samples, and is increasingly being studied as a new source of diagnostic information. Aim: This study aimed to evaluate whether analysis of Lactate levels in saliva can substitute for that of Lactate levels in blood. Methods/Materials: We processed saliva samples and serum samples from septic shock and non-septic shock patients. We found out Lactate levels in both the group. We plotted the concentration of Lactate in non-septic and septic patients and compared lactate levels in saliva to its levels in blood.Statistical analysis: Results were statistically analyzed by independent sample t test and A Spearman rho correlation. Results: We found increased serum and salivary Lactate levels in all cases of sepsis compared to the control group. Notably, the increase in Lactate levels was higher in serum as compared to saliva in septic patients, suggesting saliva may not serve as a better indicator of sepsis compared to blood. Salivary lactate was more in septic shock patients compared to non-septic shock patients. Conclusions: To our knowledge, this is the first study to compare lactic acid levels in serum and saliva in cases of sepsis. The increase in serum lactate in patients with sepsis is evident when compared to increase in salivary lactate, so serum lactate level would be easier for physicians to differentiate septic patients from non-septic patients. Salivary lactate may not serve as better indicator in septic shock patients.

The Accidental Ally: Nucleosome Barriers Can Accelerate Cohesin-Mediated Loop Formation in Chromatin.

An important question in the context of the three-dimensional organization of chromosomes is the mechanism of formation of large loops between distant basepairs. Recent experiments suggest that the formation of loops might be mediated by loop extrusion factor proteins such as cohesin. Experiments on cohesin have shown that cohesins walk diffusively on the DNA and that nucleosomes act as obstacles to the diffusion, lowering the permeability and hence reducing the effective diffusion constant. An estimation of the times required to form the loops of typical sizes seen in Hi-C experiments using these low-effective-diffusion constants leads to times that are unphysically large. The puzzle then is the following: how does a cohesin molecule diffusing on the DNA backbone achieve speeds necessary to form the large loops seen in experiments? We propose a simple answer to this puzzle and show that although at low densities, nucleosomes act as barriers to cohesin diffusion, beyond a certain concentration they can reduce loop formation times because of a subtle interplay between the nucleosome size and the mean linker length. This effect is further enhanced on considering stochastic binding kinetics of nucleosomes on the DNA backbone and leads to predictions of lower loop formation times than might be expected from a naive obstacle picture of nucleosomes.

The Possibility and Cause of Relapse After Previously Recovering From COVID-19: A Systematic Review.

The severe acute respiratory distress syndrome coronavirus-2 (SARS-Cov-2) is a novel coronavirus that is believed to be mainly transmitted via droplet and contact transmission. While research is focusing on epidemiology, transmission, vaccine development, and therapeutics for coronavirus disease 2019 (COVID-19), there is a possibility of disease relapse. There are reports of patients who tested positive for SARS-Cov-2 after clinical recovery and initial clearance of the virus. Objective This systematic review aims to identify the trends of COVID-19 relapse, the effects of co-morbidities on it, and associated mortality rates. Methods We conducted a systematic search during March and April 2020 for research articles on the relapse of COVID-19 using two primary databases, PubMed and Embase. Results A total of 13 eligible studies were screened of which 11 (case reports) were eligible for data extraction. The earliest to report relapse was after two days of discharge and the latest was 22 days after discharge. The mean number of days to relapse was 12 days and the median number was seven days. There was incomplete information about comorbidities. No mortalities were reported at the time of the study.

Caffeine as a Neoadjuvant Therapy in Parathyroid Adenomas: A Narrative Review.

Caffeine is the most used central nervous system stimulant drug to date. Many studies have shown the association of caffeine with bone remodeling, urinary calcium excretion, kidney stones, acid peptic disease, and the development of cancer. However, there has been very little research exploring the association between caffeine use and parathyroid gland disorders. We shed light on the possible connection between caffeine and parathyroid adenomas, as suggested in the literature.

Unequal Lives: A Sociodemographic Analysis of Covid19 Transmission and Mortality in India

The hierarchy of social structures shape, in very particular and measurable ways, the differential impact that a disease has on different parts of society. In this study, we use district-level disease data to perform an ecological analysis of Covid19 outcomes in India vis a vis the local socioeconomic gradient. Average doubling times and case fatality ratios have been quantified as measures of transmission and mortality, respectively, and association analysis performed with twenty variables of socioeconomic vulnerability. Persistent patterns are observed between disease outcome and social inequality, linking poor living conditions to a faster spread, an elderly populace to a slower spread, and both a college education and the presence of medical facilities to low fatality rates.