THE INFLUENCE OF MUSCULAR ACTIVATION PROFILES ON LOWER LIMB BIOMECHANICS DURING A SPORT-SPECIFIC LANDING TASK

The purpose of this study was to identify the muscular activation profiles utilised by female athletes during a sport-specific landing task, and examine the effects of varying profiles on biomechanical anterior cruciate ligament (ACL) injury risk factors. Muscular activation profiles were identified from electromyography data using a combination of principal component and cluster analysis methods, with the neuromuscular and biomechanical characteristics of profiles compared. Various muscular activation characteristics contributed to the presence of lower limb biomechanical patterns consistent with ACL injury risk factors. Reduction of ACL injury risk may be achieved by targeting these muscular activation characteristics via neuromuscular training programs

The E3 Ubiquitin Ligase SCF(Cyclin F) Transmits AKT Signaling to the Cell-Cycle Machinery

The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate. Cyclin F expression oscillates throughout the cell cycle, a rare feature among the 69 human F-box proteins, and all of its known substrates are involved in proliferation. AKT phosphorylation of cyclin F enhances its stability and promotes assembly into productive E3 ligase complexes. Importantly, expression of mutant versions of cyclin F that cannot be phosphorylated by AKT impair cell-cycle entry. Our data suggest that cyclin F transmits mitogen signaling through AKT to the core cell-cycle machinery. This discovery has potential implications for proliferative control in malignancies where AKT is activated

APC/C and SCF cyclin F Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry

The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/C(Cdh1) plays an important role in restricting S-phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box). We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. These data indicate that the coordinated, temporal ordering of cyclin F and Cdh1 degradation, organized in a double-negative feedback loop, represents a fundamental aspect of cell-cycle control. This mutual antagonism could be a feature of other oscillating systems

Self-oligomerization Regulates Stability of Survival Motor Neuron Protein Isoforms by Sequestering an SCF\u3csup\u3eSlmb\u3c/sup\u3e Degron

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

In silico APC/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase and critical regulator of cell cycle progression. Despite its vital role, it has remained challenging to globally map APC/C substrates. By combining orthogonal features of known substrates, we predicted APC/C substrates in silico. This analysis identified many known substrates and suggested numerous candidates. Unexpectedly, chromatin regulatory proteins are enriched among putative substrates, and we show experimentally that several chromatin proteins bind APC/C, oscillate during the cell cycle, and are degraded following APC/C activation, consistent with being direct APC/C substrates. Additional analysis revealed detailed mechanisms of ubiquitylation for UHRF1, a key chromatin regulator involved in histone ubiquitylation and DNA methylation maintenance. Disrupting UHRF1 degradation at mitotic exit accelerates G1-phase cell cycle progression and perturbs global DNA methylation patterning in the genome. We conclude that APC/C coordinates crosstalk between cell cycle and chromatin regulatory proteins. This has potential consequences in normal cell physiology, where the chromatin environment changes depending on proliferative state, as well as in disease. Copyright

Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCF^Slmb degron

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes

Potenziali effetti della consociazione tra genotipi di Vitis: osservazioni in vivaio

È necessario intraprendere una via maggiormente ecosostenibile e vantaggiosa per gestire le problematiche presenti in vivaio, e in generale in vigneto, adottando tecniche ammesse in agricoltura biologica o, meglio ancora, con una visione agroecologica della gestione. Le osservazioni condotte presso i Vivai Maiorana hanno indagato la diversa suscettibilità di genotipi di vite ai principali patogeni fungini e gli effetti della consociazione sui sintomi causati da tali patogeni. In primo luogo si è osservata la differenza di suscettibilità tra le cultivars di Merlot e la varietà portinnesto Kober 5BB. I genotipi di Vitis vinifera analizzati si sono dimostrati suscettibili, a differenza del portinnesto Kober 5BB che è risultato completamente esente da sintomi. In seguito, le osservazioni si sono concentrate nel lotto del barbatellaio, in cui tre filari di Calabrese e tre filari di Nerello Mascalese sono separati da un filare di Isabella. Le osservazioni svolte hanno permesso di indagare gli effetti della consociazione, sfruttando l’attuale impostazione del vivaio, in cui diversi genotipi di vite vengono coltivate a stretto contatto. Si è osservata una variazione dei sintomi di peronospora su Vitis vinifera in relazione alla distanza dalla varietà Isabella. L’effetto è presumibilmente mediato da VOCs specifici. Questi benefici, se opportunamente sfruttati, consentirebbero di ridurre sensibilmente la necessità di intervenire con prodotti esogeni nella gestione del barbatellaio, aumentando la possibilità di impostare una produzione biologica che soddisfi le necessità della viticoltura moderna, con vantaggi agronomici ed ecologici

Reconceptualizing Cross-Cutting Political Expression on Social Media : A Case Study of Facebook Comments During the 2016 Brexit Referendum

Political communication research has long sought to understand the effects of cross-cutting exposure on political participation. Here, we argue for a paradigm shift that acknowledges the agency of citizens as producers of cross-cutting expression on social media. We define cross-cutting expression as political communication through speech or behavior within a counter-attitudinal space. After explicating our conceptualization of cross-cutting expression, we empirically explore: its extent, its relationship to political arguments, and its implications for digital campaigning during the 2016 Brexit Referendum. Our dataset, comprising 2,198,741 comments from 344,884 users, is built from Facebook comments to three public campaign pages active during the Brexit referendum: StrongerIn, VoteLeave, and LeaveEU. We utilize reactions data to sort partisans into “Remain” and “Brexit” camps and, thereafter, chart users’ commenting flows across the three pages. We estimate 29% of comments to be cross-cutting, and we find strong correlations between cross-cutting expression and reasoned political arguments. Then, to better understand how cross-cutting expression may influence political participation on social media, we topic model the dataset to identify the political themes discussed during the Brexit debate on Facebook. Our findings suggest that political Facebook pages are not echo chambers, that cross-cutting expression correlates with reasoned political arguments, and that cross-cutting expression may influence the online voter mobilization potential of political Facebook pages

The influence of muscular activation profiles on lower limb biomechanics during a sport-specific landing task

The purpose of this study was to identify the muscular activation profiles utilised by female athletes during a sport-specific landing task, and examine the effects of varying profiles on biomechanical anterior cruciate ligament (ACL) injury risk factors. Muscular activation profiles were identified from electromyography data using a combination of principal component and cluster analysis methods, with the neuromuscular and biomechanical characteristics of profiles compared. Various muscular activation characteristics contributed to the presence of lower limb biomechanical patterns consistent with ACL injury risk factors. Reduction of ACL injury risk may be achieved by targeting these muscular activation characteristics via neuromuscular training programs