Condensate interfaces can accelerate protein aggregation.

Protein aggregates, formed from the assembly of aberrant, misfolded proteins, are a hallmark of neurodegenerative diseases. Disease-associated aggregates such as mutant Huntingtin polyQ inclusions, are typically enriched in p62/SQSTM1, an oligomeric protein that binds to and sequesters aberrant proteins. p62 has been suggested to sequester proteins through formation of liquid-like biomolecular condensates, but the physical mechanisms by which p62 condensates may regulate pathological protein aggregation remain unclear.

Postfasciotomy Classification System for Acute Compartment Syndrome of the Leg.

Objective: Acute compartment syndrome (ACS) is a true emergency. Even with urgent fasciotomy, there is often muscle damage and need for further surgery. Although ACS is not uncommon, no validated classification system exists to aid in efficient and clear communication.

Poly(GR) interacts with key stress granule factors promoting its assembly into cytoplasmic inclusions.

C9orf72 repeat expansions are the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly(GR) proteins are toxic to neurons by forming cytoplasmic inclusions that sequester RNA-binding proteins including stress granule (SG) proteins. However, little is known of the factors governing poly(GR) inclusion formation.

Reamed compared with unreamed nailing of tibial shaft fractures: Does the initial method of nail insertion influence outcome in patients requiring reoperations?

Background: Patients with a tibial shaft fracture experiencing their first postoperative complication following treatment with intramedullary nails may be at greater risk of subsequent complications than the whole population. We aimed to determine whether the initial method of nail insertion influences outcome in patients with a tibial shaft fracture requiring multiple reoperations.

Methods: Using the Study to Prospectively Evaluate Reamed Intramedullary Nails in Tibial Shaft Fractures trial data, we categorized patients as those not requiring reoperation, those requiring a single reoperation and those requiring multiple reoperations, and we compared them by nail insertion technique (reamed v.

DnaJC7 specifically regulates tau seeding.

Neurodegenerative tauopathies are caused by accumulation of toxic tau protein assemblies. This appears to involve template-based seeding events, whereby tau monomer changes conformation and is recruited to a growing aggregate. Several large families of chaperone proteins, including Hsp70s and J domain proteins (JDPs), cooperate to regulate the folding of intracellular proteins such as tau, but the factors that coordinate this activity are not well known.

Size distributions of intracellular condensates reflect competition between coalescence and nucleation.

Phase separation of biomolecules into condensates has emerged as a mechanism for intracellular organization and affects many intracellular processes, including reaction pathways through the clustering of enzymes and pathway intermediates. Precise and rapid spatiotemporal control of reactions by condensates requires tuning of their sizes. However, the physical processes that govern the distribution of condensate sizes remain unclear.

DnaJC7 specifically regulates tau seeding.

Neurodegenerative tauopathies are caused by accumulation of toxic tau protein assemblies. This appears to involve template-based seeding events, whereby tau monomer changes conformation and is recruited to a growing aggregate. Several large families of chaperone proteins, including Hsp70s and J domain proteins (JDPs) cooperate to regulate the folding of intracellular proteins such as tau, but the factors that coordinate this activity are not well known.

The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system.

Amyloid-like aggregates of the microtubule-associated protein Tau are associated with several neurodegenerative disorders including Alzheimer's disease. The existence of cellular machinery for the removal of such aggregates has remained unclear, as specialized disaggregase chaperones are thought to be absent in mammalian cells. Here we show in cell culture and in neurons that the hexameric ATPase valosin-containing protein (VCP) is recruited to ubiquitylated Tau fibrils, resulting in their efficient disaggregation.

Factors Predictive of Early Complications Following Total Ankle Arthroplasty.

Background: The safety of outpatient total ankle arthroplasty (TAA), and factors predictive of early complications are poorly understood. The objective of this study was to determine the frequency of early complications in patients undergoing outpatient TAA compared to a matched inpatient TAA cohort. Factors predictive of early complications following TAA are elucidated.

Preoperative photography improves patient satisfaction following hallux valgus surgery.

Background: Patient satisfaction is variable following hallux valgus (HV) surgery. This prospective, blinded, randomized trial endeavored to determine whether showing patients a preoperative photograph would improve satisfaction following HV corrective surgery.

Methods: Adult patients undergoing HV surgery were randomized to a picture group (P) or a no picture group (NP).

Nucleation landscape of biomolecular condensates.

All structures within living cells must form at the right time and place. This includes condensates such as the nucleolus, Cajal bodies and stress granules, which form via liquid-liquid phase separation of biomolecules, particularly proteins enriched in intrinsically disordered regions (IDRs). In non-living systems, the initial stages of nucleated phase separation arise when thermal fluctuations overcome an energy barrier due to surface tension.

Early radiographic outcomes following deltoid ligament repair in bimalleolar equivalent ankle fractures.

Background: Indications for deltoid ligament repair in bimalleolar equivalent ankle fractures are unclear. This study compared radiographic outcomes in bimalleolar equivalent ankle fractures undergoing open reduction internal fixation (ORIF) +/- deltoid ligament repair.

Methods: A retrospective review of 1024 ankle fractures was performed.

High-Energy Transsyndesmotic Ankle Fracture Dislocation-Injury Characteristics, Radiographic Outcomes, and Factors Affecting the Rate of Posttraumatic Arthritis in Logsplitter Injuries.

Objectives: To investigate patient demographics, injury characteristics, radiographic outcomes, and identify risk factors for developing posttraumatic arthritis in high-energy transsyndesmotic ankle fracture dislocations or "logsplitter" injuries.

Design: Retrospective cohort study.

Setting: Academic level one trauma center.

Impact of centre volume, surgeon volume, surgeon experience and geographic location on reoperation after intramedullary nailing of tibial shaft fractures.

Background: Tibial shaft fractures are the most common long-bone injury, with a reported annual incidence of more than 75 000 in the United States. This study aimed to determine whether patients with tibial fractures managed with intramedullary nails experience a lower rate of reoperation if treated at higher-volume hospitals, or by higher-volume or more experienced surgeons.

Methods: The Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT) was a multicentre randomized clinical trial comparing reamed and nonreamed intramedullary nailing on rates of reoperation to promote fracture union, treat infection or preserve the limb in patients with open and closed fractures of the tibial shaft.

Impaction fractures of the anterior tibial plafond: Outcomes after fractures around the ankle: Is the anterior impaction plafond fracture a problem?

Objectives: To determine whether patients with AO/OTA 43-B anterior impaction tibial plafond fractures have worse clinical outcomes, and an increased risk of progression to ankle arthrodesis.

Design: Retrospective cohort study.

Setting: Level 1 academic trauma center.

SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation.

Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients.

Anatomic Repair vs Closed Reduction of the Syndesmosis.

Background: The goal of the study was to compare radiographic and functional outcomes between conventional closed syndesmotic reduction and screw fixation with open reduction, direct repair of the anterior inferior tibiofibular ligament (AiTFL) and screw fixation. We hypothesized that open reduction with restoration of the AiTFL would provide an improved reduction with better radiographic and functional outcomes.

Methods: Fifty consecutive patients with OTA 44-C ankle fractures were enrolled.

Composition-dependent thermodynamics of intracellular phase separation.

Intracellular bodies such as nucleoli, Cajal bodies and various signalling assemblies represent membraneless organelles, or condensates, that form via liquid-liquid phase separation (LLPS). Biomolecular interactions-particularly homotypic interactions mediated by self-associating intrinsically disordered protein regions-are thought to underlie the thermodynamic driving forces for LLPS, forming condensates that can facilitate the assembly and processing of biochemically active complexes, such as ribosomal subunits within the nucleolus. Simplified model systems have led to the concept that a single fixed saturation concentration is a defining feature of endogenous LLPS, and has been suggested as a mechanism for intracellular concentration buffering.

Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization.

Liquid-liquid phase separation (LLPS) mediates formation of membraneless condensates such as those associated with RNA processing, but the rules that dictate their assembly, substructure, and coexistence with other liquid-like compartments remain elusive. Here, we address the biophysical mechanism of this multiphase organization using quantitative reconstitution of cytoplasmic stress granules (SGs) with attached P-bodies in human cells. Protein-interaction networks can be viewed as interconnected complexes (nodes) of RNA-binding domains (RBDs), whose integrated RNA-binding capacity determines whether LLPS occurs upon RNA influx.

Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome.

Phase transitions involving biomolecular liquids are a fundamental mechanism underlying intracellular organization. In the cell nucleus, liquid-liquid phase separation of intrinsically disordered proteins (IDPs) is implicated in assembly of the nucleolus, as well as transcriptional clusters, and other nuclear bodies. However, it remains unclear whether and how physical forces associated with nucleation, growth, and wetting of liquid condensates can directly restructure chromatin.

Biomechanics-Hot Topics Part I.

This study summarizes presentations of a symposium on biomechanically related hot topics of the 2015 Basic Science Focus Forum. Each topic emphasizes a biomechanical challenge common to all 4 of these presentations: an ideal fixation technique should deliver ample stability and sufficient flexibility to prevent fixation failure and to restore normal function.

The CNS in inbred transgenic models of 4-repeat Tauopathy develops consistent tau seeding capacity yet focal and diverse patterns of protein deposition.

Background: MAPT mutations cause neurodegenerative diseases such as frontotemporal dementia but, strikingly, patients with the same mutation may have different clinical phenotypes.

Methods: Given heterogeneities observed in a transgenic (Tg) mouse line expressing low levels of human (2 N, 4R) P301L Tau, we backcrossed founder stocks of mice to C57BL/6Tac, 129/SvEvTac and FVB/NJ inbred backgrounds to discern the role of genetic versus environmental effects on disease-related phenotypes.

Results: Three inbred derivatives of a TgTau founder line had similar quality and steady-state quantity of Tau production, accumulation of abnormally phosphorylated 64-68 kDa Tau species from 90 days of age onwards and neuronal loss in aged Tg mice.