GRASP negatively regulates the secretion of the virulence factor gp63 in Leishmania.

Metalloprotease-gp63 is a virulence factor secreted by Leishmania. However, secretory pathway in Leishmania is not well defined. Here, we cloned and expressed the GRASP homolog from Leishmania. We found that Leishmania expresses one GRASP homolog of 58 kDa protein (LdGRASP) which localizes in LdRab1- and LPG2-positive Golgi compartment in Leishmania. LdGRASP was found to bind with COPII complex, LdARF1, LdRab1 and LdRab11 indicating its role in ER and Golgi transport in Leishmania. To determine the function of LdGRASP, we generated LdGRASP knockout parasites using CRISPR-Cas9. We found fragmentation of Golgi in Ld:GRASPKO parasites. Our results showed enhanced transport of non-GPI-anchored gp63 to the cell surface leading to higher secretion of this form of gp63 in Ld:GRASPKO parasites in comparison to Ld:WT cells. In contrast, we found that transport of GPI-anchored gp63 to the cell surface is blocked in Ld:GRASPKO parasites and thereby inhibits its secretion. The overexpression of dominant-negative mutant of LdRab1 or LdSar1 in Ld:GRASPKO parasites significantly blocked the secretion of non-GPI-anchored gp63. Interestingly, we found that survival of transgenic parasites overexpressing Ld:GRASP-GFP is significantly compromised in macrophages in comparison to Ld:WT and Ld:GRASPKO parasites. These results demonstrated that LdGRASP differentially regulates Ldgp63 secretory pathway in Leishmania.

Accelerated free-breathing liver fat and R 2 * quantification using multi-echo stack-of-radial MRI with motion-resolved multidimensional regularized reconstruction: Initial retrospective evaluation.

PURPOSE: To improve image quality, mitigate quantification biases and variations for free-breathing liver proton density fat fraction (PDFF) and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ quantification accelerated by radial k-space undersampling. METHODS: A free-breathing multi-echo stack-of-radial MRI method was developed with compressed sensing with multidimensional regularization. It was validated in motion phantoms with reference acquisitions without motion and in 11 subjects (6 patients with nonalcoholic fatty liver disease) with reference breath-hold Cartesian acquisitions. Images, PDFF, and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ maps were reconstructed using different radial view k-space sampling factors and reconstruction settings. Results were compared with reference-standard results using Bland-Altman analysis. Using linear mixed-effects model fitting (p < 0.05 considered significant), mean and SD were evaluated for biases and variations of PDFF and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , respectively, and coefficient of variation on the first echo image was evaluated as a surrogate for image quality. RESULTS: Using the empirically determined optimal sampling factor of 0.25 in the accelerated in vivo protocols, mean differences and limits of agreement for the proposed method were [-0.5; -33.6, 32.7] s-1 for R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and [-1.0%; -5.8%, 3.8%] for PDFF, close to those of a previous self-gating method using fully sampled radial views: [-0.1; -27.1, 27.0] s-1 for R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and [-0.4%; -4.5%, 3.7%] for PDFF. The proposed method had significantly lower coefficient of variation than other methods (p < 0.001). Effective acquisition time of 64 s or 59 s was achieved, compared with 171 s or 153 s for two baseline protocols with different radial views corresponding to sampling factor of 1.0. CONCLUSION: This proposed method may allow accelerated free-breathing liver PDFF and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ mapping with reduced biases and variations.

A cilia-bound unconventional secretory pathway for Drosophila odorant receptors.

BACKGROUND: Post-translational transport is a vital process which ensures that each protein reaches its site of function. Though most do so via an ordered ER-to-Golgi route, an increasing number of proteins are now shown to bypass this conventional secretory pathway. RESULTS: In the Drosophila olfactory sensory neurons (OSNs), odorant receptors (ORs) are trafficked from the ER towards the cilia. Here, we show that Or22a, a receptor of various esters and alcoholic compounds, reaches the cilia partially through unconventional means. Or22a frequently present as puncta at the somatic cell body exit and within the dendrite prior to the cilia base. These rarely coincide with markers of either the intermediary ER-Golgi-intermediate-compartment (ERGIC) or Golgi structures. ERGIC and Golgi also displayed axonal localization biases, a further indication that at least some measure of OR transport may occur independently of their involvement. Additionally, neither the loss of several COPII genes involved in anterograde trafficking nor ERGIC itself affected puncta formation or Or22a transport to the cilium. Instead, we observed the consistent colocalization of Or22a puncta with Grasp65, the sole Drosophila homolog of mammalian GRASP55/Grh1, a marker of the unconventional pathway. The numbers of both Or22a and Grasp65-positive puncta were furthermore increased upon nutritional starvation, a condition known to enhance Golgi-bypassing secretory activity. CONCLUSIONS: Our results demonstrate an alternative route of Or22a transport, thus expanding the repertoire of unconventional secretion mechanisms in neurons.

The grasp reflex in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To investigate the prevalence and intensity of grasp reflexes and to examine changes in these reflexes after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: We enrolled 147 patients with probable iNPH. A standard procedure was used to determine the presence of grasp reflexes, and the intensity of these reflexes was assessed using a four-category classification. Clinical rating scales and their correlation with grasp reflexes were also evaluated. Grasp reflexes were reassessed in 72 patients 1 year after surgery. RESULTS: We found that approximately 50.3% of patients with iNPH exhibited a positive grasp reflex. Among these patients, 69% exhibited bilateral positivity, while the remaining patients showed unilateral positivity. Furthermore, the intensity of the grasp reflex was significantly correlated with the severity of gait and with cognitive, urinary, motor, and behavioural symptoms. Surgical interventions led to a reduction (41.7%) or maintenance (30.6%) of the reflex intensity in 72.3% of iNPH patients. The changes in reflex intensity showed significant positive correlations with changes in the number of steps of the Timed Up and Go test and Trail Making Test-A scores but not with changes in total scores on the iNPH Grading Scale. CONCLUSION: This retrospective study identified grasp reflexes as a highly prevalent phenomenon in patients with iNPH. These reflexes can assist in evaluating the severity of various symptoms, including cognitive, gait, urinary, motor and emotional symptoms.

Multimodal fusion of EMG and vision for human grasp intent inference in prosthetic hand control.

Objective: For transradial amputees, robotic prosthetic hands promise to regain the capability to perform daily living activities. Current control methods based on physiological signals such as electromyography (EMG) are prone to yielding poor inference outcomes due to motion artifacts, muscle fatigue, and many more. Vision sensors are a major source of information about the environment state and can play a vital role in inferring feasible and intended gestures. However, visual evidence is also susceptible to its own artifacts, most often due to object occlusion, lighting changes, etc. Multimodal evidence fusion using physiological and vision sensor measurements is a natural approach due to the complementary strengths of these modalities. Methods: In this paper, we present a Bayesian evidence fusion framework for grasp intent inference using eye-view video, eye-gaze, and EMG from the forearm processed by neural network models. We analyze individual and fused performance as a function of time as the hand approaches the object to grasp it. For this purpose, we have also developed novel data processing and augmentation techniques to train neural network components. Results: Our results indicate that, on average, fusion improves the instantaneous upcoming grasp type classification accuracy while in the reaching phase by 13.66% and 14.8%, relative to EMG (81.64% non-fused) and visual evidence (80.5% non-fused) individually, resulting in an overall fusion accuracy of 95.3%. Conclusion: Our experimental data analyses demonstrate that EMG and visual evidence show complementary strengths, and as a consequence, fusion of multimodal evidence can outperform each individual evidence modality at any given time.

Unveiling the invisible: receivers use object weight cues for grip force planning in handover actions.

Handover actions are part of our daily lives. Whether it is the milk carton at the breakfast table or tickets at the box office, we usually perform these joint actions without much conscious attention. The individual actions involved in handovers, that have already been studied intensively at the level of individual actions, are grasping, lifting, and transporting objects. Depending on the object's properties, actors must plan their execution in order to ensure smooth and efficient object transfer. Therefore, anticipatory grip force scaling is crucial. Grip forces are planned in anticipation using weight estimates based on experience or visual cues. This study aimed to investigate whether receivers are able to correctly estimate object weight by observing the giver's kinematics. For this purpose, handover actions were performed with 20 dyads, manipulating the participant role (giver/receiver) and varying the size and weight of the object. Due to the random presentation of the object weight and the absence of visual cues, the participants were unaware of the object weight from trial to trial. Kinematics were recorded with a motion tracking system and grip forces were recorded with customized test objects. Peak grip force rates were used as a measure of anticipated object weight. Results showed that receiver kinematics are significantly affected by object weight. The peak grip force rates showed that receivers anticipate object weight, but givers not. This supports the hypothesis that receivers obtain information about the object weight by observing giver's kinematics and integrating this information into their own action execution.

High-resolution free-breathing hepatobiliary phase MRI of the liver using XD-GRASP.

PURPOSE: To evaluate the performance of high-resolution free-breathing (FB) hepatobiliary phase imaging of the liver using the eXtra-Dimension Golden-angle RAdial Sparse Parallel (XD-GRASP) MRI technique. METHODS: Fifty-eight clinical patients (41 males, mean age = 52.9 ± 12.9) with liver lesions who underwent dynamic contrast-enhanced MRI with a liver-specific contrast agent were prospectively recruited for this study. Both breath-hold volumetric interpolated examination (BH-VIBE) imaging and FB imaging were performed during the hepatobiliary phase. FB images were acquired using a stack-of-stars golden-angle radial sequence and were reconstructed using the XD-GRASP method. Two experienced radiologists blinded to acquisition schemes independently scored the overall image quality, liver edge sharpness, hepatic vessel clarity, conspicuity of lesion, and overall artifact level of each image. The non-parametric paired two-tailed Wilcoxon signed-rank test was used for statistical analysis. RESULTS: Compared to BH-VIBE images, XD-GRASP images received significantly higher scores (P < 0.05) for the liver edge sharpness (4.83 ± 0.45 vs 4.29 ± 0.46), the hepatic vessel clarity (4.64 ± 0.67 vs 4.15 ± 0.56) and the conspicuity of lesion (4.75 ± 0.53 vs 4.31 ± 0.50). There were no significant differences (P > 0.05) between BH-VIBE and XD-GRASP images for the overall image quality (4.61 ± 0.50 vs 4.74 ± 0.47) and the overall artifact level (4.13 ± 0.44 vs 4.05 ± 0.61). CONCLUSION: Compared to conventional BH-VIBE MRI, FB radial acquisition combined with XD-GRASP reconstruction facilitates higher spatial resolution imaging of the liver during the hepatobiliary phase. This enhancement can significantly improve the visualization and evaluation of the liver.

Peripheral nerve blocks of wrist and finger flexors can increase hand opening in chronic hemiparetic stroke.

Introduction: Hand opening is reduced by abnormal wrist and finger flexor activity in many individuals with stroke. This flexor activity also limits hand opening produced by functional electrical stimulation (FES) of finger and wrist extensor muscles. Recent advances in electrical nerve block technologies have the potential to mitigate this abnormal flexor behavior, but the actual impact of nerve block on hand opening in stroke has not yet been investigated. Methods: In this study, we applied the local anesthetic ropivacaine to the median and ulnar nerve to induce a complete motor block in 9 individuals with stroke and observed the impact of this block on hand opening as measured by hand pentagonal area. Volitional hand opening and FES-driven hand opening were measured, both while the arm was fully supported on a haptic table (Unloaded) and while lifting against gravity (Loaded). Linear mixed effect regression (LMER) modeling was used to determine the effect of Block. Results: The ropivacaine block allowed increased hand opening, both volitional and FES-driven, and for both unloaded and loaded conditions. Notably, only the FES-driven and Loaded condition's improvement in hand opening with the block was statistically significant. Hand opening in the FES and Loaded condition improved following nerve block by nearly 20%. Conclusion: Our results suggest that many individuals with stroke would see improved hand-opening with wrist and finger flexor activity curtailed by nerve block, especially when FES is used to drive the typically paretic finger and wrist extensor muscles. Such a nerve block (potentially produced by aforementioned emerging electrical nerve block technologies) could thus significantly address prior observed shortcomings of FES interventions for individuals with stroke.

i-MYO: A multi-grasp prosthetic hand control system based on gaze movements, augmented reality, and myoelectric signals.

BACKGROUND: Controlling a multi-grasp prosthetic hand still remains a challenge. This study explores the influence of merging gaze movements and augmented reality in bionics on improving prosthetic hand control. METHODS: A control system based on gaze movements, augmented reality, and myoelectric signals (i-MYO) was proposed. In the i-MYO, the GazeButton was introduced into the controller to detect the grasp-type intention from the eye-tracking signals, and the proportional velocity scheme based on the i-MYO was used to control hand movement. RESULTS: The able-bodied subjects with no prior training successfully transferred objects in 91.6% of the cases and switched the optimal grasp types in 97.5%. The patient could successfully trigger the EMG to control the hand holding the objects in 98.7% of trials in around 3.2 s and spend around 1.3 s switching the optimal grasp types in 99.2% of trials. CONCLUSIONS: Merging gaze movements and augmented reality in bionics can widen the control bandwidth of prosthetic hand. With the help of i-MYO, the subjects can control a prosthetic hand using six grasp types if they can manipulate two muscle signals and gaze movement.

Evolution of the ribbon-like organization of the Golgi apparatus in animal cells.

The "ribbon," a structural arrangement in which Golgi stacks connect to each other, is considered to be restricted to vertebrate cells. Although ribbon disruption is linked to various human pathologies, its functional role in cellular processes remains unclear. In this study, we investigate the evolutionary origin of the Golgi ribbon. We observe a ribbon-like architecture in the cells of several metazoan taxa suggesting its early emergence in animal evolution predating the appearance of vertebrates. Supported by AlphaFold2 modeling, we propose that the evolution of Golgi reassembly and stacking protein (GRASP) binding by golgin tethers may have driven the joining of Golgi stacks resulting in the ribbon-like configuration. Additionally, we find that Golgi ribbon assembly is a shared developmental feature of deuterostomes, implying a role in embryogenesis. Overall, our study points to the functional significance of the Golgi ribbon beyond vertebrates and underscores the need for further investigations to unravel its elusive biological roles.

Decoding of unimanual and bimanual reach-and-grasp actions from EMG and IMU signals in persons with cervical spinal cord injury.

Objective. Chronic motor impairments of arms and hands as the consequence of a cervical spinal cord injury (SCI) have a tremendous impact on activities of daily life. A considerable number of people however retain minimal voluntary motor control in the paralyzed parts of the upper limbs that are measurable by electromyography (EMG) and inertial measurement units (IMUs). An integration into human-machine interfaces (HMIs) holds promise for reliable grasp intent detection and intuitive assistive device control.Approach. We used a multimodal HMI incorporating EMG and IMU data to decode reach-and-grasp movements of groups of persons with cervical SCI (n = 4) and without (control, n = 13). A post-hoc evaluation of control group data aimed to identify optimal parameters for online, co-adaptive closed-loop HMI sessions with persons with cervical SCI. We compared the performance of real-time, Random Forest-based movement versus rest (2 classes) and grasp type predictors (3 classes) with respect to their co-adaptation and evaluated the underlying feature importance maps.Main results. Our multimodal approach enabled grasp decoding significantly better than EMG or IMU data alone (p<0.05). We found the 0.25 s directly prior to the first touch of an object to hold the most discriminative information. Our HMIs correctly predicted 79.3 ± STD 7.4 (102.7 ± STD 2.3 control group) out of 105 trials with grand average movement vs. rest prediction accuracies above 99.64% (100% sensitivity) and grasp prediction accuracies of 75.39 ± STD 13.77% (97.66 ± STD 5.48% control group). Co-adaption led to higher prediction accuracies with time, and we could identify adaptions in feature importances unique to each participant with cervical SCI.Significance. Our findings foster the development of multimodal and adaptive HMIs to allow persons with cervical SCI the intuitive control of assistive devices to improve personal independence.

Movement analysis of the distal transverse arch of the dominant hand while grasping and pinching objects: A descriptive, correlational research study.

BACKGROUND: The distal transverse arches obtained from active and passive motions of the hand and the used range of motion (u-ROM) of the hand arch in activities of daily living have rarely been reported. PURPOSE: This study aimed to investigate the distal transverse arch angle of the dominant hand, the influence of age, and the u-ROM of the arch when grasping and pinching objects. STUDY DESIGN: Descriptive and correlational research design. METHODS: The active and passive distal transverse arches of the dominant hand of 104 healthy subjects were measured using a goniometer. Additionally, the hand arch was measured when the subjects grasped and pinched objects. These data were used to analyze the correlation with age and to calculate the u-ROM (u-ROM %) rate of the distal transversal arch. Furthermore, the u-ROM% between the ring and fifth finger components of the hand arch was compared. RESULTS: The active and passive dorsal arch angles were 135.8 (10.0°) and 169.9 (11.5°), respectively. The distal transverse arch angle tended to decline with age (active: r = -0.18, p = 0.07, 95% confidence interval = -0.36 to 0.02; passive: r = -0.40, p ≤ 0.001, 95% confidence interval = -0.55 to -0.23). The u-ROM% of the hand arch in grasping and pinching ranged from 65.5 (9.8)% to 84.6 (11.6)% and from 52.1 (7.9)% to 67.4 (9.1)%, respectively, against active and passive motions. The ring finger component was significantly higher than the fifth finger component (active: p = 0.08 to <0.001, effect size = -0.17 to -0.69; passive: p ≤ 0.001, effect size= -0.71 to -0.86). A similar trend was observed in both men and women. CONCLUSIONS: Therapists should evaluate the movement of the distal transverse arch of the injured hand in detail and consider the age, sex, and component of the hand arch when intervening.

Ceramide-1-phosphate is a regulator of Golgi structure and is co-opted by the obligate intracellular bacterial pathogen Anaplasma phagocytophilum.

Many intracellular pathogens structurally disrupt the Golgi apparatus as an evolutionarily conserved promicrobial strategy. Yet, the host factors and signaling processes involved are often poorly understood, particularly for Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. We found that A. phagocytophilum elevated cellular levels of the bioactive sphingolipid, ceramide-1-phosphate (C1P), to promote Golgi fragmentation that enables bacterial proliferation, conversion from its non-infectious to infectious form, and productive infection. A. phagocytophilum poorly infected mice deficient in ceramide kinase, the Golgi-localized enzyme responsible for C1P biosynthesis. C1P regulated Golgi morphology via activation of a PKCα/Cdc42/JNK signaling axis that culminates in phosphorylation of Golgi structural proteins, GRASP55 and GRASP65. siRNA-mediated depletion of Cdc42 blocked A. phagocytophilum from altering Golgi morphology, which impaired anterograde trafficking of trans-Golgi vesicles into and maturation of the pathogen-occupied vacuole. Cells overexpressing phosphorylation-resistant versions of GRASP55 and GRASP65 presented with suppressed C1P- and A. phagocytophilum-induced Golgi fragmentation and poorly supported infection by the bacterium. By studying A. phagocytophilum, we identify C1P as a regulator of Golgi structure and a host factor that is relevant to disease progression associated with Golgi fragmentation.IMPORTANCECeramide-1-phosphate (C1P), a bioactive sphingolipid that regulates diverse processes vital to mammalian physiology, is linked to disease states such as cancer, inflammation, and wound healing. By studying the obligate intracellular bacterium Anaplasma phagocytophilum, we discovered that C1P is a major regulator of Golgi morphology. A. phagocytophilum elevated C1P levels to induce signaling events that promote Golgi fragmentation and increase vesicular traffic into the pathogen-occupied vacuole that the bacterium parasitizes. As several intracellular microbial pathogens destabilize the Golgi to drive their infection cycles and changes in Golgi morphology is also linked to cancer and neurodegenerative disorder progression, this study identifies C1P as a potential broad-spectrum therapeutic target for infectious and non-infectious diseases.

The contribution of semantic distance knowledge to size constancy in perception and grasping when visual cues are limited.

To achieve a stable perception of object size in spite of variations in viewing distance, our visual system needs to combine retinal image information and distance cues. Previous research has shown that, not only retinal cues, but also extraretinal sensory signals can provide reliable information about depth and that different neural networks (perception versus action) can exhibit preferences in the use of these different sources of information during size-distance computations. Semantic knowledge of distance, a purely cognitive signal, can also provide distance information. Do the perception and action systems show differences in their ability to use this information in calculating object size and distance? To address this question, we presented 'glow-in-the-dark' objects of different physical sizes at different real distances in a completely dark room. Participants viewed the objects monocularly through a 1-mm pinhole. They either estimated the size and distance of the objects or attempted to grasp them. Semantic knowledge was manipulated by providing an auditory cue about the actual distance of the object: "20 cm", "30 cm", and "40 cm". We found that semantic knowledge of distance contributed to some extent to size constancy operations during perceptual estimation and grasping, but size constancy was never fully restored. Importantly, the contribution of knowledge about distance to size constancy was equivalent between perception and action. Overall, our study reveals similarities and differences between the perception and action systems in the use of semantic distance knowledge and suggests that this cognitive signal is useful but not a reliable depth cue for size constancy under restricted viewing conditions.

Ultra-rapid, Free-breathing, Real-time Cardiac Cine MRI Using GRASP Amplified with View Sharing and KWIC Filtering.

Purpose To achieve ultra-high temporal resolution (approximately 20 msec) in free-breathing, real-time cardiac cine MRI using golden-angle radial sparse parallel (GRASP) reconstruction amplified with view sharing (VS) and k-space-weighted image contrast (KWIC) filtering. Materials and Methods Fourteen pediatric patients with congenital heart disease (mean age [SD], 9 years ± 2; 13 male) and 10 adult patients with arrhythmia (mean age, 62 years ± 8; nine male) who underwent both standard breath-hold cine and free-breathing real-time cine using GRASP were retrospectively identified. To achieve high temporal resolution, each time frame was reconstructed using six radial spokes, corresponding to acceleration factors ranging from 24 to 32. To compensate for loss in spatial resolution resulting from over-regularization in GRASP, VS and KWIC filtering were incorporated. The blur metric, visual image quality scores, and biventricular parameters were compared between clinical and real-time cine images. Results In pediatric patients, the incorporation of VS and KWIC into GRASP (ie, GRASP + VS + KWIC) produced significantly (P < .05) sharper x-y-t (blur metric: 0.36 ± 0.03, 0.41 ± 0.03, 0.48 ± 0.03, respectively) and x-y-f (blur metric: 0.28 ± 0.02, 0.31 ± 0.03, 0.37 ± 0.03, respectively) component images compared with GRASP + VS and conventional GRASP. Only the noise score differed significantly between GRASP + VS + KWIC and clinical cine; all visual scores were above the clinically acceptable (3.0) cutoff point. Biventricular volumetric parameters strongly correlated (R2 > 0.85) between clinical and real-time cine images reconstructed with GRASP + VS + KWIC and were in good agreement (relative error < 6% for all parameters). In adult patients, the visual scores of all categories were significantly lower (P < .05) for clinical cine compared with real-time cine with GRASP + VS + KWIC, except for noise (P = .08). Conclusion Incorporating VS and KWIC filtering into GRASP reconstruction enables ultra-high temporal resolution (approximately 20 msec) without significant loss in spatial resolution. Keywords: Cine, View Sharing, k-Space-weighted Image Contrast Filtering, Radial k-Space, Pediatrics, Arrhythmia, GRASP, Compressed Sensing, Real-Time, Free-Breathing Supplemental material is available for this article. © RSNA, 2024.

Effects of binocular cue availability on leaping performance in Cheirogaleus medius: implications for primate origins.

Multiple competing hypotheses attribute the evolution of the suite of traits that distinguish primates from their closest relatives, including forward-facing eyes, which create a wide field of binocular vision, to specific behavioral and ecological factors. The grasp-leaping hypothesis suggests that the evolution of these traits in basal primates was driven by the demands of a form of leaping locomotion unique to primates. Whether the grasp-leaping hypothesis provides a viable mechanism for the evolution of primates' forward-facing eyes remains untested. To determine whether grasp-leaping locomotion may have contributed to driving the evolution of primates' forward-facing eyes, the importance of vision within the binocular field for this type of leaping was evaluated experimentally in Cheirogaleus medius, one of the cheirogaleid primate species considered reasonable living analogs of the earliest primates. Availability of binocular visual cues was experimentally restricted using a head-mounted blinder that narrowed the binocular visual field without altering the total visual field. Animals altered their launch behavior, reduced their horizontal leap speed, and were significantly more likely to select paths that offered the shortest available leaps when their binocular field was restricted. Restriction of binocular cue availability also significantly increased the probability of adverse landings even when statistically controlling for potentially confounding variables such as leap distance, horizontal leap speed, learning effects, etc. These results suggest a functional mechanism by which selection for improved grasp-leaping could also have contributed to the evolution of forward-facing eyes in the earliest crown primates.

Assessing hand grasp in patients with systemic sclerosis using the 16-grasp test: Preliminary results from a multidisciplinary study group.

BACKGROUND: Reports on hand dysfunction and rehabilitation in SSc are quite scarce in the literature and mainly focus on functional assessment tools, such as the Duruoz Hand Index and the HAMIS test for evaluating hand mobility by simulating specific grasps with nine different objects. PURPOSE OF THE STUDY: This study aimed to provide an adequate assessment methodology for hand grasp dysfunctions in patients suffering from systemic sclerosis (SSc) through the 16-grasp test. STUDY DESIGN: Case-control study. METHODS: Ninety-seven consecutive SSc patients were recruited at our Scleroderma Unit, where a 16-grasp test was performed by all patients and supervised by an experienced hand therapist. Sixteen different patterns of grasp have been divided into power grasps and precision pinch and two more modalities: static and dynamic prehension evaluation on scale from 0 to 4. We also compared previous evaluations on 19 of patients recruited. RESULTS: The majority of SSc patients (84 females and 13 males; mean age 56.0±12.0 years; mean disease duration 8.0±6.0 years) displayed grasp dysfunctions; in particular 48% and 54% reported slight difficulty in the right and left grasps respectively, 6% medium difficulty in both hands, and only 3% and 1% experienced severe difficulty respectively, while 31.5% had no issues in either hand. Our results showed that the limited cutaneous subset (lcSSc) scored a lower deficit for either grasp compared to diffuse form (dcSSc). No statistically significant differences in total grasp deficit had been noticed when comparing patients having a disease duration < 5 years or longer. In the retrospective study on 19 of these patients, 8 out of 10 lcSSc patients showed no significant changes, while in 2 out of 10, slight improvements were observed in both hands. However, in the dcSSc group, 4 out of 9 worsened bilaterally while the grasp scores for 5 of them remained unchanged. CONCLUSION: Our study reported hand involvement in both lcSSc and dcSSc forms, more significantly in dcSSc patients. This test is intended to be a more objective means of assessing grasp alterations linked to scleroderma hand deformities. Furthermore, thanks to its intuitiveness, the test may be useful for engineers designing personalized ergonomic assistive devices.

Porcine reproductive and respiratory syndrome virus triggers Golgi apparatus fragmentation-mediated autophagy to facilitate viral self-replication.

Macroautophagy/autophagy is a cellular degradation and recycling process that maintains the homeostasis of organisms. A growing number of studies have reported that autophagy participates in infection by a variety of viruses. Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe financial losses to the global swine industry. Although much research has shown that PRRSV triggers autophagy for its own benefits, the exact molecular mechanisms involved in PRRSV-triggered autophagy remain to be fully elucidated. In the current study, we demonstrated that PRRSV infection significantly induced Golgi apparatus (GA) fragmentation, which promoted autophagy to facilitate viral self-replication. Mechanistically, PRRSV nonstructural protein 2 was identified to interact with and degrade the Golgi reassembly and stacking protein 65 dependent on its papain-like cysteine protease 2 activity, resulting in GA fragmentation. Upon GA fragmentation, GA-resident Ras-like protein in brain 2 was disassociated from Golgi matrix protein 130 and subsequently bound to unc-51 like autophagy activating kinase 1 (ULK1), which enhanced phosphorylation of ULK1 and promoted autophagy. Taken together, all these results expand the knowledge of PRRSV-triggered autophagy as well as PRRSV pathogenesis to support novel potential avenues for prevention and control of the virus. More importantly, these results provide the detailed mechanism of GA fragmentation-mediated autophagy, deepening the understanding of autophagic processes.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) infection results in a serious swine disease affecting pig farming worldwide. Despite that numerous studies have shown that PRRSV triggers autophagy for its self-replication, how PRRSV induces autophagy is incompletely understood. Here, we identify that PRRSV Nsp2 degrades GRASP65 to induce GA fragmentation, which dissociates RAB2 from GM130 and activates RAB2-ULK1-mediated autophagy to enhance viral replication. This work expands our understanding of PRRSV-induced autophagy and PRRSV replication, which is beneficial for anti-viral drug development.

Emerging roles of O-GlcNAcylation in protein trafficking and secretion.

The emerging roles of O-GlcNAcylation, a distinctive post-translational modification, are increasingly recognized for their involvement in the intricate processes of protein trafficking and secretion. This modification exerts its influence on both conventional and unconventional secretory pathways. Under healthy and stress conditions, such as during diseases, it orchestrates the transport of proteins within cells, ensuring timely delivery to their intended destinations. O-GlcNAcylation occurs on key factors, like coat protein complexes (COPI and COPII), clathrin, SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), and GRASP55 (Golgi reassembly stacking protein of 55 kDa) that control vesicle budding and fusion in anterograde and retrograde trafficking and unconventional secretion. The understanding of O-GlcNAcylation offers valuable insights into its critical functions in cellular physiology and the progression of diseases, including neurodegeneration, cancer, and metabolic disorders. In this review, we summarize and discuss the latest findings elucidating the involvement of O-GlcNAc in protein trafficking and its significance in various human disorders.

Robot Grasp Planning: A Learning from Demonstration-Based Approach.

Robot grasping constitutes an essential capability in fulfilling the complexities of advanced industrial operations. This field has been extensively investigated to address a range of practical applications. However, the generation of a stable grasp remains challenging, principally due to the constraints imposed by object geometries and the diverse objectives of the tasks. In this work, we propose a novel learning from demonstration-based grasp-planning framework. This framework is designed to extract crucial human grasp skills, namely the contact region and approach direction, from a single demonstration. Then, it formulates an optimization problem that integrates the extracted skills to generate a stable grasp. Distinct from conventional methods that rely on learning implicit synergies through human demonstration or on mapping the dissimilar kinematics between human hands and robot grippers, our approach focuses on learning the intuitive human intent that involves the potential contact regions and the grasping approach direction. Furthermore, our optimization formulation is capable of identifying the optimal grasp by minimizing the surface fitting error between the demonstrated contact regions on the object and the gripper finger surface and imposing a penalty for any misalignment between the demonstrated and the gripper's approach directions. A series of experiments is conducted to verify the effectiveness of the proposed algorithm through both simulations and real-world scenarios.