Closure Movement Research Articles

Structure of the human dopamine transporter and mechanisms of inhibition

The neurotransmitter dopamine has central roles in mood, appetite, arousal and movement1. Despite its importance in brain physiology and function, and as a target for illicit and therapeutic drugs, the human dopamine transporter (hDAT) and mechanisms by which it is inhibited by small molecules and Zn2+ are without a high-resolution structural context. Here we determine the structure of hDAT in a tripartite complex with the competitive inhibitor and cocaine analogue, (–)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane2 (β-CFT), the non-competitive inhibitor MRS72923 and Zn2+ (ref. 4). We show how β-CFT occupies the central site, approximately halfway across the membrane, stabilizing the transporter in an outward-open conformation. MRS7292 binds to a structurally uncharacterized allosteric site, adjacent to the extracellular vestibule, sequestered underneath the extracellular loop 4 (EL4) and adjacent to transmembrane helix 1b (TM1b), acting as a wedge, precluding movement of TM1b and closure of the extracellular gate. A Zn2+ ion further stabilizes the outward-facing conformation by coupling EL4 to EL2, TM7 and TM8, thus providing specific insights into how Zn2+ restrains the movement of EL4 relative to EL2 and inhibits transport activity.

Development of the hyolaryngeal architecture in horseshoe bats: insights into the evolution of the pulse generation for laryngeal echolocation

BackgroundThe hyolaryngeal apparatus generates biosonar pulses in the laryngeally echolocating bats. The cartilage and muscles comprising the hyolarynx of laryngeally echolocating bats are morphologically modified compared to those of non-bat mammals, as represented by the hypertrophied intrinsic laryngeal muscle. Despite its crucial contribution to laryngeal echolocation, how the development of the hyolarynx in bats differs from that of other mammals is poorly documented. The genus Rhinolophus is one of the most sophisticated laryngeal echolocators, with the highest pulse frequency in bats. The present study provides the first detailed description of the three-dimensional anatomy and development of the skeleton, cartilage, muscle, and innervation patterns of the hyolaryngeal apparatus in two species of rhinolophid bats using micro-computed tomography images and serial tissue sections and compares them with those of laboratory mice. Furthermore, we measured the peak frequency of the echolocation pulse in active juvenile and adult individuals to correspond to echolocation pulses with hyolaryngeal morphology at each postnatal stage.ResultsWe found that the sagittal crests of the cricoid cartilage separated the dorsal cricoarytenoid muscle in horseshoe bats, indicating that this unique morphology may be required to reinforce the repeated closure movement of the glottis during biosonar pulse emission. We also found that the cricothyroid muscle is ventrally hypertrophied throughout ontogeny, and that the cranial laryngeal nerve has a novel branch supplying the hypertrophied region of this muscle. Our bioacoustic analyses revealed that the peak frequency shows negative allometry against skull growth, and that the volumetric growth of all laryngeal cartilages is correlated with the pulse peak frequency.ConclusionsThe unique patterns of muscle and innervation revealed in this study appear to have been obtained concomitantly with the acquisition of tracheal chambers in rhinolophids and hipposiderids, improving sound intensity during laryngeal echolocation. In addition, significant protrusion of the sagittal crest of the cricoid cartilage and the separated dorsal cricoarytenoid muscle may contribute to the sophisticated biosonar in this laryngeally echolocating lineage. Furthermore, our bioacoustic data suggested that the mineralization of these cartilages underpins the ontogeny of echolocation pulse generation. The results of the present study provide crucial insights into how the anatomy and development of the hyolaryngeal apparatus shape the acoustic diversity in bats.

Trends in Ukraine's foreign trade in the context of complicated international transportation

Introduction. Over the past ten years, there has been a decline in the effectiveness of multilateral cooperation agreements within the WTO, resulting in the growing importance of bilateral trade agreements. The EU countries and the UK are among the most important geographical areas for deepening bilateral cooperation with Ukraine, which has been favourably influenced by trade liberalisation as a result of the signing of the Association Agreement between Ukraine and the European Union and the implementation of the Deep and Comprehensive Free Trade Agreement. Improved terms of trade between Ukraine and Europe, despite the war in Ukraine, ensured positive dynamics of trade turnover, but the commodity structure has undergone significant changes. Recently, a trade embargo was imposed on agricultural products, and the border was closed for the transportation of products through Poland and other countries. In this regard, it is an urgent scientific task to determine the impact of the complication of transport. As well as identifying trends in the further development of foreign trade with partner countries. The purpose of the paper is to іdentificate the changes in export sales routes, as well as trends in Ukraine's foreign economic activity in the context of more complicated international transport. Results. The importance for Ukraine's economy of expanding the scope of foreign economic relations with European countries based on international transport is determined. The author emphasises a number of economic prerequisites and advantages of foreign economic relations between Ukraine and European countries, which determine the trends in the development of foreign trade. The author identifies the important role of continuing institutional and structural reforms in our country, which should be intensified and aimed at strengthening the competitive potential of the national economy. The main stages of integration of foreign economic relations between Ukraine and European countries are highlighted. It is proved that there is a high potential of European integration for the Ukrainian economy. However, in the current conditions of complicated movement of goods and closure of borders by partner countries, this direction of development of the national economy is considered as the main one, with certain difficulties, which will slow down the pace of socio-economic growth and restore the lost. Conclusion. By establishing international economic and trade relations and sales channels, Ukraine's foreign trade can develop and function effectively. National economies of different countries interact through the establishment of diplomatic relations, cooperation agreements, and the creation of intergovernmental associations. After analysing all the factors, it can be argued that establishing economic and political ties with the world's leading countries and increasing the level of foreign trade is possible by stepping up efforts in the most promising sectors of the global economy. Foreign economic and trade relations contribute to the growth of the national economy, acceleration of scientific and technological progress, and improvement of living standards.

Effects of Covid-19 on smallholder tobacco farmers in Zimbabwe

Zimbabwe is an agricultural based economy contributing an average 20% to the gross domestic product (GDP). The sector has been facing a number of challenges including low productivity, erratic rainfall, poor soil fertility, low investment, shortages of farm power, poor physical and institutional infrastructure. Tobacco is one of the major crops grown in Zimbabwe normally accounting for more than 50% of agricultural exports, 30% of total exports and nearly 10% of GDP. The advent of COVID-19 significantly affected tobacco production. The government instituted measures such as restrictions on transportation and movement of people, lockdowns, curfews, limited gatherings and closure of schools and universities. The study investigated the effects of COVID-19 on smallholder tobacco farmers in Zimbabwe. The results revealed both positive and negative effects of COVID-19 on tobacco farmers. On the positive side, there has been an increased adoption of information communication technology among farmers. The negative effects of the COVID-19 included reduction in tobacco hectarage, distortions in supply chains, shortage of labour supply, increased cost of production and difficulty in accessing extension services. Extension workers were also not able to offer training to farmers, negatively affecting new tobacco farmers given that they had limited know-how on cultivation of the crop and to, later on, cure it. The non-contracted farmers adopted coping and resilience strategies that ensured that they minimised losses and debts. These farmers were worried about the persistence of the pandemic and how long it would take them to take their produce to the markets. The implication of the study is that shocks to the agriculture sector have serious ramifications on farmers and the downstream industries. There is need for the government to build resilient mechanisms for the farmers and ensure timely bailouts so that production and marketing are not disturbed. Key words: Tobacco, Value Chains, COVID-19, Pandemic, Smallholder Farmers, Contract, No-Contract, Hectarage

Timing of smile suppression during the articulation of labials in smiled speech

Past studies have shown that opposing forces on the lips can be reconciled by suppressing a smile during speech-related lip closure movements [Liu et al., 2020, ISSP]. However, the exact timing of this suppression on the smiling posture remains unknown. The purpose of this study was to determine the onset and duration of smile suppression during labial production in smiled speech. We collected video footage of participants reading sentences that contain labial sounds (/m, f, v, b, p, w/) under three facial posture conditions (neutral, smile, laugh), and extracted short video clips of the labial sound productions. We then analyzed the extent of lip spreading in each facial posture condition using OpenFace 2.0 [Baltrušaitis et al., 2018, IEEE]. Our preliminary results show that smile is suppressed in the smiling and laughing conditions, with attenuation beginning approximately 300ms prior to labial sound production, and continuing for about 600ms regardless of conditions. Further analysis will investigate the duration of suppression after the offset of labials and will be conducted on more participants.

Reversible domain closure modulates GlnBP ligand binding affinity.

Glutamine binding protein (GlnBP) is an Escherichia Coli periplasmic binding protein, which binds and carries glutamine to the inner membrane ATP-binding cassette (ABC) transporter. GlnBP binds the ligand with affinity around 0.1μM measured by isothermal titration calorimetry (ITC) and ligand binding stabilizes protein structure shown by its increase in thermodynamic stability. However, the molecular determinant of GlnBP ligand binding is not known. Electrostatic and hydrophobic interaction between GlnBP and glutamine are critical factors. We propose that the freedome of closure movement is also vital for ligand binding. In order to approve this hypothesis, we generate a series of mutants with different linker length that has different magnitude of domain closure. Mutants show different ligand binding affinity, which indicates that the propensity of domain closure determines the ligand binding affinity. Ligand binding triggers gradual ensemble conformational change. Structural changes upon ligand binding are monitored by combination of small angle x-ray scattering (SAXS) and NMR spectroscopy. Detailed structure characterization of GlnBP contributes to a better understanding of ligand binding and provides the structural basis for biosensor design.

Genome-Wide Identification of Cotton (Gossypium spp.) Glycerol-3-Phosphate Dehydrogenase (GPDH) Family Members and the Role of GhGPDH5 in Response to Drought Stress.

Glycerol-3-phosphate dehydrogenase (GPDH) is a key enzyme in plant glycerol synthesis and metabolism, and plays an important role in plant resistance to abiotic stress. Here, we identified 6, 7, 14 and 14 GPDH genes derived from Gossypium arboreum, Gossypium raimondii, Gossypium barbadense and Gossypium hirsutum, respectively. Phylogenetic analysis assigned these genes into three classes, and most of the genes within the family were expanded by whole-genome duplication (WGD) and segmental duplications. Moreover, determination of the nonsynonymous substitution rate/synonymous substitution rate (Ka/Ks) ratio showed that the GPDH had an evolutionary preference for purifying selection. Transcriptome data revealed that GPDH genes were more active in the early stages of fiber development. Additionally, numerous stress-related cis-elements were identified in the potential promoter region. Then, a protein–protein-interaction (PPI) network of GPDH5 in G. hirsutum was constructed. In addition, we predicted 30 underlying miRNAs in G. hirsutum. Functional validation results indicated that silencing GhGPDH5 diminished drought tolerance in the upland cotton TM-1 line. In summary, this study provides a fundamental understanding of the GPDH gene family in cotton, GhGPDH5 exerts a positive effect during drought stress and is potentially involved in stomatal closure movements.

Facial nerve regeneration using silicone conduits filled with ammonia-functionalized graphene oxide and frankincense-embedded hydrogel

BackgroundSilicone tube (ST) conduits have been accepted as a therapeutic alternative to direct nerve suturing in the treatment of nerve injuries; however, the search for optimal adjuncts to maximize the outcomes is still ongoing. Frankincense (Fr) and graphene oxide (GO) have both been cited as neuroregenerative compounds in the literature. This study assesses the efficacy of these materials using a ST conduit in a rat facial nerve motor neuron axotomy model, distal to the stylomastoid foramen.MethodsAmmonia-functionalized graphene oxide (NH2-GO) and/or Fr extract were embedded in a collagen-chitosan hydrogel and were injected inside a ST. The ST was inserted in the gap between the axotomized nerve stumps. Return of function in eye closure, blinking reflex, and vibrissae movements were assessed and compared to control groups through 30 days following axotomy. To assess the histological properties of regenerated nerves, biopsies were harvested distal to the axotomy site and were visualized through light and fluorescence microscopy using LFB and anti-MBP marker, respectively.ResultsThere was no significant difference in behavioral test results between groups. Histological analysis of the nerve sections revealed increased number of regenerating axons and mean axon diameter in NH2-GO group and decreased myelin surface area in Fr group. Using both NH2-GO and Fr resulted in increased number of regenerated axons and myelin thickness compared to the hydrogel group.ConclusionsThe findings suggest a synergistic effect of the substances above in axon regrowth, notably in myelin regeneration, where Fr supposedly decreases myelin synthesis.

Evolution from a social animal to a virtual animal? using new tech and AI during and Post-COVID-19 crisis period

“Man is by nature a social animal” proclaimed Aristotle. This characteristic has made us organize into complex hierarchical societies where individuals are interdependent to satisfy basic necessities. Although we all know that social distancing is the most effective way to contain the spread of coronavirus, this is something biologically unnatural for humans.1 In this health emergency, many governments have decided to impose strict measures to limit social interactions to an absolute minimum. Lockdowns, limitations of movement of people and closure of borders have all been necessary measures for the good of societies.

Dynamic Fast Imaging Employing Steady State Acquisition Magnetic Resonance Imaging of the Vocal Tract in One Overtone Male Singer: Our Preliminary Experience

To demonstrate physiological changing of vocal tract's structures during overtone singing with commercial magnetic resonance imaging (MRI) Fast Imaging Employing Steady State Acquisition (FIESTA) dynamic sequence. A 1.5 T MRI with a 16 channel head-and-neck coil and a FIESTA sequence were used. A temporal resolution of 0.155 sec (7 image/s). A single professional singer was studied. The MR acquisition is made while the singer performed a predetermined singing sequence. Three different overtone singing techniques were examined (L-technique, J-technique, and NG technique) and one effect (Ezengileer) applied to L-technique. For each overtone technique we evaluated MRI movement of lips, tongue, velopharyngeal closure, and relationship among tongue and pharyngeal posterior wall/soft palate. To cancel the noise over-imposed, the dynamic MRI was subsequently dubbed in studio with the audio of the preset overtone sing. Dubbed MR images were analyzed with an Overtone Analyzer Software and different sound frequencies were identified and pointed out as colored lines. This study shows that different overtone techniques are related to a specific conformation of tongue, lips, soft and hard palate and motion's relation changing between them. Only a correct conformation of vocal tract's structure allows resonance and so to hear desired fundamental and harmonic pitch in overtone singing. The preliminary data of our study demonstrates that FIESTA dynamic MRI sequence can be used to depict changing of position of vocal tract's structure in overtone singing techniques with a good temporal and anatomic resolution.

Design of Multiple Wearable Robotic Extra Fingers for Human Hand Augmentation

Augmenting the human hand with robotic extra fingers is a cutting-edge research topic and has many potential applications, in particular as a compensatory and rehabilitation tool for patients with upper limb impairments. Devices composed of two extra fingers are preferred with respect to single finger devices when reliable grasps, resistance to external disturbances, and higher payloads are required. Underactuation and compliance are design choices that can reduce the device complexity and weight, maintaining the adaptability to different grasped objects. When only one motor is adopted to actuate multiple fingers, a differential mechanism is necessary to decouple finger movements and distribute forces. In this paper, the main features of a wearable device composed of two robotic extra fingers are described and analyzed in terms of kinematics, statics, and mechanical resistance. Each finger is composed of modular phalanges and is actuated with a single tendon. Interphalangeal joints include a passive elastic element that allows restoring the initial reference configuration when the tendon is released. The stiffness of each passive element can be customized in the manufacturing process and can be chosen according to a desired closure movement of the fingers. Another key aspect of the device is the differential system connecting the actuator to the fingers.

Investigation of the perception characteristics of multiple impact sounds occurring from the manipulation of electronic devices

Electronic devices must be quiet during manipulation for operations. In addition, the sounds need to show distinct impression to satisfy the user’s auditory experience and indicate the completion of an operation. The sounds occur in a short time from frictional contact and the consequent structural vibration when a user operates a device. In this study, the impact sound during printer cassette insertion is analyzed. The rail vibration during closure movement generates continuous sound. This movement ends with the impact sound from contact between the cassette and printer body. The sounds occur as clicking sounds with double impacts separated by a short interval. This clicking sound is important serving as an indicator of completed insertion. The user’s perception of this complex sound is investigated. A physical index to quantify the generated sound is proposed to assist comparisons between printers. Prony’s method was used to characterize the sound features including duration, double impact interval, magnitudes, and decay rates. From the extracted features, artificial clicking sounds were simulated for sound quality evaluations. Auditory experiments were performed to investigate the user’s preference for the separated rail and impact noises. The just noticeable difference was defined to classify the important factors influencing the perception characteristics.

Design of Soft Robotic Actuation for Supporting Eyelid Closure Movement.

We have been developing a facial wearable robot to support the eyelid movements of patients with facial paralysis, especially on one side of the face [1]. This robot has a mechanism for supporting eyelid movements, made from a soft material, which is called the eyelid gating mechanism (ELGM). The ELGM deforms by simple rotational actuation inputs and its deformation is customized to the eyelid movements. Therefore, this robot can provide non-invasive and gentle support for eyelid movements. We herein describe the design rule of the ELGM, and based on this, we conducted a deformation analysis with a non-linear finite element method. We verified the deformation trend from the results, and developed three prototypes based on this trend. Using these prototypes, we conducted a clinical study with facial paralysis patients to evaluate if the ELGM is capable of assisting in closing the eyelid.

Lip closure training improves eating behaviors and prefrontal cortical hemodynamic activity and decreases daytime sleep in elderly persons

Previous research suggests that aging-related deterioration of oral functions causes not only eating/swallowing disorders but also various conditions such as sleep disorders and higher-order brain dysfunction. The aim of the present study was to examine the effects of lip closure training on eating behavior, sleep, and brain function in elderly persons residing in an elder care facility. The 20 elderly subjects (mean age, 86.3 ± 1.0 years) were assigned to a control group or a lip closure training (LCT) group, in which an oral rehabilitation device was used for daily LCT sessions over a 4-week period. Before and after the 4-week intervention period, maximal lip closure force was measured, and prefrontal cortical hemodynamic activity (changes in oxygenated hemoglobin concentration) during lip closure movements was measured with (LCT group) or without (control group) use of the oral rehabilitation device. We also analyzed eating behavior and daytime sleep before and after the intervention period.Compared with the control group, the LCT group showed improved maximal lip closure force, shortened eating time, decreased food spill rates, and decreased daytime sleeping. Furthermore, compared with the control group, the LCT group showed a significant increase in prefrontal cortical activity during lip closure. In addition, the increase rate in the right dorsolateral prefrontal cortical activity after the intervention period was significantly correlated with the increase rate in the maximal lip closure force after the intervention period.These findings suggest that LCT is useful in elderly individuals with decreased eating/oral and cognitive functions without the risk of pulmonary aspiration during training.

Laterality of proprioception in the orofacial muscles and temporomandibular joint

Laterality of function in the orofacial musculature suggests there may be side-to-side asymmetry of proprioceptive acuity in lip movement compared to the temporomandibular joint (TMJ). In the present work, 14 young adults were tested for acuity of lip and TMJ closure movements onto plugs varying from 5 to 8mm without visual feedback. Testing was conducted on both left and right sides, using the same psychophysical task and stimuli. Results showed superior proprioceptive acuity at the lips, with no significant side effect. However, there was side-to-side asymmetry in the correlations between proprioceptive performance for the two anatomical structures, with performance on the right side strongly correlated but not on the left. This is consistent with the need for coordination between structures during chewing. When acuity at different points in the stimulus range was examined, the right side lips were better with small stimuli. Overall, results support enhanced use-specific proprioception.

HUW BEYNON: MARXISMO E SOCIOLOGIA

Resumo A entrevista com o sociólogo britânico Huw Beynon, autor de Trabalhando para a Ford, entrelaça as dinâmicas de trajetória intelectual, desenvolvimento institucional da sociologia (do trabalho, em particular), da política britânica e da tradição marxista. O autor reflete sobre uma vasta experiência na construção e difusão de uma sociologia crítica, centrada no engajamento com seu objeto e público extra- acadêmico. Destacam-se aqui as experiências em educação de adultos e de extensão com trabalhadores, as primeiras expressões da globalização e neoliberalismo como "movimento de fechamento" de fábricas - assim como as reações acadêmicas e sindicais ao processo -, além de respostas político-culturais recentes acerca da preservação de uma identidade operária enraizada e da reconstrução do Partido Trabalhista em torno da adesão da juventude. A entrevista com Huw Beynon sintetiza os elementos de uma obra que é parte inseparável das transformações no mundo do trabalho nos últimos cinquenta anos, assim como se apresenta como inestimável para sua compreensão sociológica.

Analysis of Mining-induced Valley Closure Movements

Valley closure movements have been observed for decades in Australia and overseas when underground mining occurred beneath or in close proximity to valleys and other forms of irregular topographies. Valley closure is defined as the inward movements of the valley sides towards the valley centreline. Due to the complexity of the local geology and the interplay between several geological, topographical and mining factors, the underlying mechanisms that actually cause this behaviour are not completely understood. A comprehensive programme of numerical modelling investigations has been carried out to further evaluate and quantify the influence of a number of these mining and geological factors and their inter-relationships. The factors investigated in this paper include longwall positional factors, horizontal stress, panel width, depth of cover and geological structures around the valley. It is found that mining in a series passing beneath the valley dramatically increases valley closure, and mining parallel to valley induces much more closure than other mining orientations. The redistribution of horizontal stress and influence of mining activity have also been recognised as important factors promoting valley closure, and the effect of geological structure around the valley is found to be relatively small. This paper provides further insight into both the valley closure mechanisms and how these mechanisms should be considered in valley closure prediction models.

Evaluation of stiffness and plastic deformation of active ceramic self-ligating bracket clips after repetitive opening and closure movements.

OBJECTIVE: The aim of this study was to assess whether repetitive opening and closure of self-ligating bracket clips can cause plastic deformation of the clip. METHODS: Three types of active/interactive ceramic self-ligating brackets (n = 20) were tested: In-Ovation C, Quicklear and WOW. A standardized controlled device performed 500 cycles of opening and closure movements of the bracket clip with proper instruments and techniques adapted as recommended by the manufacturer of each bracket type. Two tensile tests, one before and one after the repetitive cycles, were performed to assess the stiffness of the clips. To this end, a custom-made stainless steel 0.40 x 0.40 mm wire was inserted into the bracket slot and adapted to the universal testing machine (EMIC DL2000), after which measurements were recorded. On the loading portion of the loading-unloading curve of clips, the slope fitted a first-degree equation curve to determine the stiffness/deflection rate of the clip. RESULTS: The results of plastic deformation showed no significant difference among bracket types before and after the 500 cycles of opening and closure (p = 0.811). There were significant differences on stiffness among the three types of brackets (p = 0.005). The WOW bracket had higher mean values, whereas Quicklear bracket had lower values, regardless of the opening/closure cycle. CONCLUSION: Repetitive controlled opening and closure movements of the clip did not alter stiffness or cause plastic deformation.

Dynamics of hERG closure allow novel insights into hERG blocking by small molecules.

Today, drug discovery routinely uses experimental assays to determine very early if a lead compound can yield certain types of off-target activity. Among such off targets is hERG. The ion channel plays a primordial role in membrane repolarization and altering its activity can cause severe heart arrhythmia and sudden death. Despite routine tests for hERG activity, rather little information is available for helping medicinal chemists and molecular modelers to rationally circumvent hERG activity. In this article novel insights into the dynamics of hERG channel closure are described. Notably, helical pairwise closure movements have been observed. Implications and relations to hERG inactivation are presented. Based on these dynamics novel insights on hERG blocker placement are presented, compared to literature, and discussed. Last, new evidence for horizontal ligand positioning is shown in light of former studies on hERG blockers.

Technology-aided recreation and communication opportunities for post-coma persons affected by lack of speech and extensive motor impairment

This study assessed technology-aided intervention programs for two post-coma men who had re-acquired consciousness, but were unable to engage in personally or socially relevant occupations, given their lack of functional speech and their extensive motor disabilities. The microswitches used for accessing the program contents consisted of (a) a pressure sensor fixed in the palm of the first man's hand that could be activated with a small hand closure movement, and (b) an optic sensor fixed under the chin of the second man that could be activated by mouth opening movements. The programs' content consisted of recreation and communication options, which involved activating music, videos, and basic requests, sending and receiving (listening to) text messages, and placing phone calls. The results showed that the men (a) used the technology-aided programs successfully to manage the recreation and communication options available and (b) showed consistent preference for the sessions with the technology-aided program over other daily events. Family and staff members interviewed about the participants' programs (seven members for each participant) thought that the participants enjoyed the intervention sessions with the programs and that the programs had beneficial effects for them. Implications of the findings are discussed.