SUMO1 hinders α-Synuclein fibrillation by inducing structural compaction.

Small Ubiquitin-like Modifier 1 (SUMO1) is an essential protein for many cellular functions, including regulation, signaling, etc., achieved by a process known as SUMOylation, which involves covalent attachment of SUMO1 to target proteins. SUMO1 also regulates the function of several proteins via non-covalent interactions involving the hydrophobic patch in the target protein identified as SUMO Binding or Interacting Motif (SBM/SIM). Here, we demonstrate a crucial functional potential of SUMO1 mediated by its non-covalent interactions with α-Synuclein, a protein responsible for many neurodegenerative diseases called α-Synucleinopathies. SUMO1 hinders the fibrillation of α-Synuclein, an intrinsically disordered protein (IDP) that undergoes a transition to ß-structures during the fibrillation process. Using a plethora of biophysical techniques, we show that SUMO1 transiently binds to the N-terminus region of α-Synuclein non-covalently and causes structural compaction, which hinders the self-association process and thereby delays the fibrillation process. On the one hand, this study demonstrates an essential functional role of SUMO1 protein concerning neurodegeneration; it also illustrates the commonly stated mechanism that IDPs carry out multiple functions by structural adaptation to suit specific target proteins, on the other. Residue-level details about the SUMO1-α-Synuclein interaction obtained here also serve as a reliable approach for investigating the detailed mechanisms of IDP functions.

Investigating the Effect of Fly Ash Addition on the Metallurgical and Mechanical Behavior of Al-Si-Mg-Cu Alloy for Engine Cylinder Head Application.

The authors researched the physical, metallurgical, and mechanical characteristics of A354 alloy (Al-Si-Mg-Cu) reinforced with 5, 10, and 15 wt% of fly ash metal matrix composites. A baseline alloy and three composites were fabricated by a liquid metallurgy route and poured into a permanent mold to obtain cast rods of dimension Φ32 mm × 156 mm. The metallurgical characterization of the developed alloy and metal matrix composites was conducted using energy-dispersive spectroscopy (EDS), field-emission scanning electron microscopy (FESEM), and X-ray diffraction. All the developed composites showed a pore-free nature, but only A354 alloy reinforced with 5 wt% of fly ash (AF5) possessed a homogeneous distribution and perfect bonding of the fly ash with the A354 matrix. Therefore, transmission electron microscopy (TEM) analysis was performed on the sample AF5. All developed alloys and metal matrix composites were subjected to hardness and mechanical property tests. It was observed that the AF5 sample had 170 ± 5.6 HV and tensile strength of 216 ± 2.3 MPa, 18.8% and 24.8% higher than the A354 matrix, but the ductility (6.5 ± 0.43%) was reduced by 23% from the baseline alloy. Finally, the fractography analysis was conducted on all the samples using FESEM to analyze the fracture mode. The fabricated 5 wt% fly ash-based metal matrix composite showed better mechanical performance than other samples. Hence, sample AF5 is suggested for manufacturing components in automotive and structural parts.

Role of non-specific interactions in the phase-separation and maturation of macromolecules.

Phase separation of biomolecules could be mediated by both specific and non-specific interactions. How the interplay between non-specific and specific interactions along with polymer entropy influences phase separation is an open question. We address this question by simulating self-associating molecules as polymer chains with a short core stretch that forms the specifically interacting functional interface and longer non-core regions that participate in non-specific/promiscuous interactions. Our results show that the interplay of specific (strength, ϵsp) and non-specific interactions (strength, ϵns) could result in phase separation of polymers and its transition to solid-like aggregates (mature state). In the absence of ϵns, the polymer chains do not dwell long enough in the vicinity of each other to undergo phase separation and transition into a mature state. On the other hand, in the limit of strong ϵns, the assemblies cannot transition into the mature state and form a non-specific assembly, suggesting an optimal range of interactions favoring mature multimers. In the scenario where only a fraction (Nfrac) of the non-core regions participate in attractive interactions, we find that slight modifications to either ϵns or Nfrac can result in dramatically altered self-assembled states. Using a combination of heterogeneous and homogeneous mix of polymers, we establish how this interplay between interaction energies dictates the propensity of biomolecules to find the correct binding partner at dilute concentrations in crowded environments.

Emerging Super-specialty of Neurology: Intraoperative Neurophysiological Monitoring (IONM) and Experience in Various Neurosurgeries at a Tertiary Care Hospital in Doha, Qatar.

Introduction Intraoperative neurophysiological monitoring (IONM) helps in better patient outcomes by minimizing risks related to the functional status of the nervous system during surgical procedures. An IONM alert to the surgical team during the surgery can help them identify the cause and take immediate corrective action. IONM confers possible benefits, including improved surgical morbidity and mortality, better patient care, minimal neurological deficits, reduced hospital stay, medical costs, and litigation risk. In addition, a highly skilled IONM team will make a better patient outcome. Methods We retrospectively reviewed 62 consecutive patients who underwent intracranial and spinal neurosurgical procedures. Multimodality IONM was utilized, including somatosensory evoked potentials, transcranial electrical motor evoked potential, spontaneous and triggered electromyography, electroencephalography, electrocorticography, cortical sensory mapping, and direct electrical cortical stimulation. Of a total of 62 patients, two patients revealed neurotonic EMG discharges during IONM, and most patients woke up without any new neurological deficit. Results Sixty-two patients were included, ranging from age 5 to 77 years (mean 43.5 years), with 54.8% men and 45.2% female. Multimodality IONM was used in all patients. Two EMG alerts were recorded during IONM, during a brain tumor resection, and right acetabular hip surgery with postoperative right foot drop. Conclusion Multimodality IONM is the gold standard of care for any surgical services and is used as real-time monitoring of functional integrity of neural structures at risk. If utilized by trained and expert teams, numerous surgeries may benefit from multimodality intraoperative neurophysiologic monitoring.

A survey of human shoulder functional kinematic representations.

In this survey, we review the field of human shoulder functional kinematic representations. The central question of this review is to evaluate whether the current approaches in shoulder kinematics can meet the high-reliability computational challenge. This challenge is posed by applications such as robot-assisted rehabilitation. Currently, the role of kinematic representations in such applications has been mostly overlooked. Therefore, we have systematically searched and summarised the existing literature on shoulder kinematics. The shoulder is an important functional joint, and its large range of motion (ROM) poses several mathematical and practical challenges. Frequently, in kinematic analysis, the role of the shoulder articulation is approximated to a ball-and-socket joint. Following the high-reliability computational challenge, our review challenges this inappropriate use of reductionism. Therefore, we propose that this challenge could be met by kinematic representations, that are redundant, that use an active interpretation and that emphasise on functional understanding.