SPECC1L binds the myosin phosphatase complex MYPT1/PP1ß and can regulate its distribution between microtubules and filamentous actin.

The subcellular localization, activity , and substrate specificity of the serine/threonine protein phosphatase 1 catalytic subunit (PP1cat) is mediated through its dynamic association with regulatory subunits in holoenzyme complexes. While some functional overlap is observed for the three human PP1cat isoforms, they also show distinct targeting based on relative preferences for specific regulatory subunits. A well-known example is the preferential association of MYPT1 with PP1ß in the myosin phosphatase complex. In smooth muscle, MYPT1/PP1ß counteracts the muscle contraction induced by phosphorylation of the light chains of myosin by the myosin light chain kinase. This phosphatase complex is also found in nonmuscle cells, where it is targeted to both myosin and nonmyosin substrates and contributes to regulation of the balance of cytoskeletal structure and motility during cell migration and division. Although it remains unclear how MYPT1/PP1ß traffics between microtubule- and actin-associated substrates, our identification of the microtubule- and actin-binding protein SPECC1L in both the PP1ß and MYPT1 interactomes suggests that it is the missing link. Our validation of their association using coimmunoprecipitation and proximity biotinylation assays, together with the strong overlap that we observed for the SPECC1L and MYPT1 interactomes, confirmed that they exist in a stable complex in the cell. We further showed that SPECC1L binds MYPT1 directly and that it can impact the balance of the distribution of the MYPT1/PP1ß complex between the microtubule and filamentous actin networks.

Identification of an FMNL2 Interactome by Quantitative Mass Spectrometry.

Formin Homology Proteins (Formins) are a highly conserved family of cytoskeletal regulatory proteins that participate in a diverse range of cellular processes. FMNL2 is a member of the Diaphanous-Related Formin sub-group, and previous reports suggest FMNL2's role in filopodia assembly, force generation at lamellipodia, subcellular trafficking, cell-cell junction assembly, and focal adhesion formation. How FMNL2 is recruited to these sites of action is not well understood. To shed light on how FMNL2 activity is partitioned between subcellular locations, we used biotin proximity labeling and proteomic analysis to identify an FMNL2 interactome. The interactome identified known and new FMNL2 interacting proteins with functions related to previously described FMNL2 activities. In addition, our interactome predicts a novel connection between FMNL2 and extracellular vesicle assembly. We show directly that FMNL2 protein is present in exosomes.

Cooperative assembly of filopodia by the formin FMNL2 and I-BAR domain protein IRTKS.

Filopodia are long finger-like actin-based structures that project out from the plasma membrane as cells navigate and explore their extracellular environment. The initiation of filopodia formation requires release of tension at the plasma membrane followed by the coordinated assembly of long unbranched actin filaments. Filopodia growth is maintained by a tip complex that promotes actin polymerization and protects the growing barbed ends of the actin fibers from capping proteins. Filopodia growth also depends on additional F-actin bundling proteins to stiffen the actin filaments as well as extension of the membrane sheath projecting from the cell periphery. These activities can be provided by a number of actin-binding and membrane-binding proteins including formins such as formin-like 2 (FMNL2) and FMNL3, and Inverse-Bin-Amphiphysin-Rvs (I-BAR) proteins such as IRTKS and IRSp53, but the specific requirement for these proteins in filopodia assembly is not clear. We report here that IRTKS and IRSp53 are FMNL2-binding proteins. Coexpression of FMNL2 with either I-BAR protein promotes cooperative filopodia assembly. We find IRTKS, but not IRSp53, is required for FMNL2-induced filopodia assembly, and FMNL2 and IRTKS are mutually dependent cofactors in this process. Our results suggest that the primary function for FMNL2 during filopodia assembly is binding to the plasma membrane and that regulation of actin dynamics by its formin homology 2 domain is secondary. From these results, we conclude that FMNL2 initiates filopodia assembly via an unexpected novel mechanism, by bending the plasma membrane to recruit IRTKS and thereby nucleate filopodia assembly.

Actin-based regulation of ciliogenesis - The long and the short of it.

The primary cilia is found on the mammalian cell surface where it serves as an antenna for the reception and transmission of a variety of cellular signaling pathways. At its core the cilium is a microtubule-based organelle, but it is clear that its assembly and function are dependent upon the coordinated regulation of both actin and microtubule dynamics. In particular, the discovery that the centrosome is able to act as both a microtubule and actin organizing centre implies that both cytoskeletal networks are acting directly on the process of cilia assembly. In this review, we set our recent results with the formin FHDC1 in the context of current reports that show each stage of ciliogenesis is impacted by changes in actin dynamics. These include direct effects of actin filament assembly on basal body positioning, vesicle trafficking to and entry into the cilium, cilia length, cilia membrane organization and cilia-dependent signaling.

Impact of fish consumption on all-cause mortality in older people with and without dementia: a community-based cohort study.

BACKGROUND: Increased fish consumption reduces the risk of dementia. However, it is unknown whether fish consumption reduced all-cause mortality in people with dementia. The purpose of the study is to investigate the association of fish consumption with all-cause mortality in older people with dementia versus those without dementia. METHODS: Using a standard method of the Geriatric Mental State, we interviewed 4165 participants aged ≥ 60 years who were randomly recruited from five provinces in China during 2007-2009 to collect the baseline data of socio-demography, disease risk factors, histories of disease, and details of dietary intakes, and diagnosed dementia (n = 406). They were followed up for vital status until 2012. RESULTS: The cohort follow-up documented 329 deaths; 61 were in participants with dementia (55.3 per 1000 person-years) and 224 were those without dementia (22.3). In all participants, the risk of all-cause mortality was reduced with fish intake at " ≥ twice a week" (multivariate-adjusted hazard ratio 0.58, 95% CI 0.34-0.96) and at "once a week or less" (0.79, 0.53-1.18) compared to "never eat" over the past two years. In participants without baseline dementia, the corresponding HRs for all-cause mortality were 0.57 (0.33-0.98) and 0.85 (0.55-1.31), while in participants with dementia were 1.36 (0.28-6.60) and 1.05 (0.30-3.66), respectively. CONCLUSION: This study reveals that consumption of fish in older age reduced all-cause mortality in older people without dementia, but not in people with dementia. Fish intake should be increased in older people in general, prior to the development of dementia in the hope of preventing dementia and prolonging life.

Seasonality of Pediatric Mental Health Emergency Department Visits, School, and COVID-19.

OBJECTIVES: The aim of this study was to explore how the academic calendar, and by extension school-year stressors, contributes to the seasonality of pediatric mental health emergency department (ED) visits. METHODS: The authors reviewed all pediatric mental health ED visits at a large urban medical center from 2014 to 2019. Patients who were younger than 18 years at time of presentation, were Durham residents, and had a primary payer of Medicaid were included in the sample population, and the dates of ED visits of the sample population were compared against dates of academic semesters and summer/winter breaks of a relevant school calendar. Of patients with multiple ED visits, only the first ED presentation was included, and descriptive statistics and a rate ratio were used to describe the study group and identify the rate of ED visits during semesters compared with breaks. RESULTS: Among the sample population from 2014 to 2019, there were 1004 first pediatric mental health ED visits. Of these ED visits, the average number of visits per week during summer/winter breaks was 2.2, and the average number of visits per week during academic semester dates was 3.4. The rate of ED visits was significantly greater during academic semesters compared with breaks (Rate Ratio, 1.6; 95% confidence interval, 1.4-2.0; P < 0.001). CONCLUSIONS: Children may be at greater risk of behavioral health crises or having increased mental needs when school is in session. As many children's mental health has worsened during the COVID-19 (coronavirus disease 2019) pandemic, these findings highlight the need for increased mental health services in the school setting as children return to in-person learning. In addition, it may benefit health systems to plan behavioral health staffing around academic calendars.

The scaffold-protein IQGAP1 enhances and spatially restricts the actin-nucleating activity of Diaphanous-related formin 1 (DIAPH1).

The actin cytoskeleton is a dynamic array of filaments that undergoes rapid remodeling to drive many cellular processes. An essential feature of filament remodeling is the spatio-temporal regulation of actin filament nucleation. One family of actin filament nucleators, the Diaphanous-related formins, is activated by the binding of small G-proteins such as RhoA. However, RhoA only partially activates formins, suggesting that additional factors are required to fully activate the formin. Here we identify one such factor, IQ motif containing GTPase activating protein-1 (IQGAP1), which enhances RhoA-mediated activation of the Diaphanous-related formin (DIAPH1) and targets DIAPH1 to the plasma membrane. We find that the inhibitory intramolecular interaction within DIAPH1 is disrupted by the sequential binding of RhoA and IQGAP1. Binding of RhoA and IQGAP1 robustly stimulates DIAPH1-mediated actin filament nucleation in vitro In contrast, the actin capping protein Flightless-I, in conjunction with RhoA, only weakly stimulates DIAPH1 activity. IQGAP1, but not Flightless-I, is required to recruit DIAPH1 to the plasma membrane where actin filaments are generated. These results indicate that IQGAP1 enhances RhoA-mediated activation of DIAPH1 in vivo Collectively these data support a model where the combined action of RhoA and an enhancer ensures the spatio-temporal regulation of actin nucleation to stimulate robust and localized actin filament production in vivo.

Impacts of depression subcase and case on all-cause mortality in older people: The findings from the multi-centre community-based cohort study in China.

OBJECTIVES: It is unclear whether and to what extent depression subcases and cases in older age were associated with all-cause mortality. Little is known about gender differences in the associations. We assess these in older Chinese. METHODS: We examined a random sample of 6124 participants aged ≥60 years across five provinces in China. They were interviewed using a standard method of the GMS-AGECAT to diagnose depression subcase and case and record sociodemographic and disease risk factors at baseline, and to follow up their vital status. We employed Cox regression models to determine all-cause mortality in relation to depression subcases and cases, with adjustment for important variables, including social support and co-morbidities. RESULTS: Over the 10-year follow-up, 928 deaths occurred. Compared to those without depression at baseline, participants with depression subcase (n = 196) and case (n = 264) had increased risk of mortality; adjusted hazard ratios (HRs) were 1.46 (95% CI 1.07-2.00) and 1.45 (1.10-1.91). The adjusted HRs in men were 1.15 (0.72-1.81) and 1.85 (1.22-2.81), and in women 1.87 (1.22-2.87) and 1.22 (0.83-1.77) respectively. In participants aged ≥65 years, the adjusted HRs were 1.12 (0.68-1.84) and 1.99 (1.28-3.10) in men, and 2.06 (1.32-2.24) and 1.41 (0.94-2.10) in women. Increased HR in depression subcases was higher in women than man (ratio of HRs was 1.84, p = 0.034). CONCLUSIONS: Older people with depression subcase could have increased all-cause mortality to a similar extent to those with depression case. More attention should be paid to subcases of depression in women to tackle gender inequalities and improve survival.

Influence of periodontal disease on risk of dementia: a systematic literature review and a meta-analysis.

Periodontal disease (PD) is common and increases cardiovascular diseases. However, it is unclear whether PD is associated with increased risk of dementia. We carried out a systematic review and meta-analysis to investigate the influence of PD on dementia. We projected the number of dementia cases to be saved by reducing PD prevalence in the world. We searched cohort and case-control studies reporting the association of PD with all dementia (or any specific type of dementia) through PubMed, MEDLINE, PsycINFO, SocINDEX, CINHAL, and CNKI until 7th November 2018. Five cohorts and seven case-control studies were identified for review. We pooled eligible data to calculate relative risk (RR) of dementia in relation to PD and computed the number of dementia cases saved through reducing PD prevalence. Of 12 studies, six were undertaken in Asia, four in Europe and two in America. Eleven studies showed a positive association between PD and the risk of dementia, of which 10 were significant, and one reported a non-significant inverse association. Overall their quality was good. Pooled RR of dementia in relation to PD from all high quality studies was 1.38 (95%CI 1.01-1.90); in the five cohorts was 1.18 (1.06-1.31) and in the two case-control studies 2.25 (1.48-3.42). A 50% reduction in the current prevalence of 20% of PD in the population could save 850,000 (630,000-1,420,000) patients with dementia in the world. PD could increase the risk of incident dementia. Preventing and treating PD could contribute to controlling the global epidemic of dementia.

A specific FMNL2 isoform is up-regulated in invasive cells.

BACKGROUND: Formins are a highly conserved family of cytoskeletal remodeling proteins. A growing body of evidence suggests that formins play key roles in the progression and spread of a variety of cancers. There are 15 human formin proteins and of these the Diaphanous-Related Formins (DRFs) are the best characterized. Included in the DRFs are the Formin-Like proteins, FMNL1, 2 & 3, each of which have been strongly implicated in driving tumorigenesis and metastasis of specific tumors. In particular, increased FMNL2 expression correlates with increased invasiveness of colorectal cancer (CRC) in vivo and for a variety of CRC cell-lines in vitro. FMNL2 expression is also required for invasive cell motility in other cancer cell-lines. There are multiple alternatively spliced isoforms of FMNL2 and it is predicted that the encoded proteins will differ in their regulation, subcellular localization and in their ability to regulate cytoskeletal dynamics. RESULTS: Using RT-PCR we identified four FMNL2 isoforms expressed in CRC and melanoma cell-lines. We find that a previously uncharacterized FMNL2 isoform is predominantly expressed in a variety of melanoma and CRC cell lines; this isoform is also more effective in driving 3D motility. Building on previous reports, we also show that FMNL2 is required for invasion in A375 and WM266.4 melanoma cells. CONCLUSIONS: Taken together, these results suggest that FMNL2 is likely to be generally required in melanoma cells for invasion, that a specific isoform of FMNL2 is up-regulated in invasive CRC and melanoma cells and this isoform is the most effective at facilitating invasion.

Bacterial subversion of host cytoskeletal machinery: hijacking formins and the Arp2/3 complex.

The host actin nucleation machinery is subverted by many bacterial pathogens to facilitate their entry, motility, replication, and survival. The majority of research conducted in the past primarily focused on exploitation of a host actin nucleator, the Arp2/3 complex, by bacterial pathogens. Recently, new studies have begun to explore the role of formins, another family of host actin nucleators, in bacterial pathogenesis. This review provides an overview of recent advances in the study of the exploitation of the Arp2/3 complex and formins by bacterial pathogens. Secreted bacterial effector proteins seem to manipulate the regulation of these actin nucleators or functionally mimic them to drive bacterial entry, motility and survival within host cells. An enhanced understanding of how formins are exploited will provide us with greater insight into how a fundamental eurkaryotic cellular process is utilized by bacteria and will also advance our knowledge of host-pathogen interactions.

The diaphanous-related formins promote protrusion formation and cell-to-cell spread of Listeria monocytogenes.

The Gram-positive bacterium Listeria monocytogenes is a facultative intracellular pathogen whose virulence depends on its ability to spread from cell to cell within an infected host. Although the actin-related protein 2/3 (Arp2/3) complex is necessary and sufficient for Listeria actin tail assembly, previous studies suggest that other actin polymerization factors, such as formins, may participate in protrusion formation. Here, we show that Arp2/3 localized to only a minor portion of the protrusion. Moreover, treatment of L. monocytogenes-infected HeLa cells with a formin FH2-domain inhibitor significantly reduced protrusion length. In addition, the Diaphanous-related formins 1-3 (mDia1-3) localized to protrusions, and knockdown of mDia1, mDia2, and mDia3 substantially decreased cell-to-cell spread of L. monocytogenes. Rho GTPases are known to be involved in formin activation. Our studies also show that knockdown of several Rho family members significantly influenced bacterial cell-to-cell spread. Collectively, these findings identify a Rho GTPase-formin network that is critically involved in the cell-to-cell spread of L. monocytogenes.

The formin FMNL3 is a cytoskeletal regulator of angiogenesis.

The process of angiogenesis requires endothelial cells (ECs) to undergo profound changes in shape and polarity. Although this must involve remodelling of the EC cytoskeleton, little is known about this process or the proteins that control it. We used a co-culture assay of angiogenesis to examine the cytoskeleton of ECs actively undergoing angiogenic morphogenesis. We found that elongation of ECs during angiogenesis is accompanied by stabilisation of microtubules and their alignment into parallel arrays directed at the growing tip. In other systems, similar microtubule alignments are mediated by the formin family of cytoskeletal regulators. We screened a library of human formins and indentified formin-like 3 (FMNL3; also known as FRL2) as a crucial regulator of EC elongation during angiogenesis. We showed that activated FMNL3 triggers microtubule alignment and that FMNL3 is required for this alignment during angiogenic morphogenesis. FMNL3 was highly expressed in the ECs of zebrafish during development and embryos that were depleted for FMNL3 showed profound defects in developmental angiogenesis that were rescued by expression of the human gene. We conclude that FMNL3 is a new regulator of endothelial microtubules during angiogenesis and is required for the conversion of quiescent ECs into their elongated angiogenic forms.

Formin-mediated actin polymerization promotes Salmonella invasion.

Salmonella invade host cells using Type 3 secreted effectors, which modulate host cellular targets to promote actin rearrangements at the cell surface that drive bacterial uptake. The Arp2/3 complex contributes to Salmonella invasion but is not essential, indicating other actin regulatory factors are involved. Here, we show a novel role for FHOD1, a formin family member, in Salmonella invasion. FHOD1 and Arp2/3 occupy distinct microdomains at the invasion site and control distinct aspects of membrane protrusion formation. FHOD1 is phosphorylated during infection and this modification is required for promoting bacterial uptake by host cells. ROCK II, but not ROCK I, is recruited to the invasion site and is required for FHOD1 phosphorylation and for Salmonella invasion. Together, our studies revealan important phospho-dependent FHOD1 actin polymerization pathway in Salmonella invasion.

The descriptive epidemiology of delirium symptoms in a large population-based cohort study: results from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).

BACKGROUND: In the general population, the epidemiological relationships between delirium and adverse outcomes are not well defined. The aims of this study were to: (1) construct an algorithm for the diagnosis of delirium using the Geriatric Mental State (GMS) examination; (2) test the criterion validity of this algorithm against mortality and dementia risk; (3) report the age-specific prevalence of delirium as determined by this algorithm. METHODS: Participant and informant data in a randomly weighted subsample of the Cognitive Function and Ageing Study were taken from a standardized assessment battery. The algorithmic definition of delirium was based on the DSM-IV classification. Outcomes were: proportional hazard ratios for death; odds ratios of dementia at 2-year follow-up. RESULTS: Data from 2197 persons (representative of 13,004) were used, median age 77 years, 64% women. Study-defined delirium was associated with a new dementia diagnosis at two years (OR 8.82, 95% CI 2.76 to 28.2) and death (HR 1.28, 95% CI 1.03 to 1.60), even after adjustment for acute illness severity. Similar associations were seen for study-defined subsyndromal delirium. Age-specific prevalence as determined by the algorithm increased with age from 1.8% in the 65-69 year age group to 10.1% in the ≥85 age group (p < 0.01 for trend). For study-defined subsyndromal delirium, age-specific period prevalence ranged from 8.2% (65-69 years) to 36.1% (≥85 years). CONCLUSIONS: These results demonstrate the possibility of constructing an algorithmic diagnosis for study-defined delirium using data from the GMS schedule, with predictive criterion validity for mortality and dementia risk. These are the first population-based analyses able to account prospectively for both illness severity and an earlier study diagnosis of dementia.

Functional disability and death wishes in older Europeans: results from the EURODEP concerted action.

PURPOSE: Physical illness has been shown to be a risk factor for suicidal behaviour in older adults. The association between functional disability and suicidal behaviour in older adults is less clear. The aim of this study was to examine the relationship between functional disability and death wishes in late life. METHODS: Data from 11 population studies on depression in persons aged 65 and above were pooled, yielding a total of 15,890 respondents. Level of functional disability was trichotomised (no, intermediate, high). A person was considered to have death wishes if the death wish/suicidal ideation item of the EURO-D scale was endorsed. Odds ratios for death wishes associated with functional disability were calculated in a multilevel logistic regression model. RESULTS: In total, 5 % of the men and 7 % of the women reported death wishes. Both intermediate (OR 1.89, 95 % CI 1.42; 2.52) and high functional disability (OR 3.22, 95 % CI 2.34; 4.42) were associated with death wishes. No sex differences could be shown. Results remained after adding depressive symptoms to the model. CONCLUSIONS: Functional disability was independently associated with death wishes in older adults. Results can help inform clinicians who care for older persons with functional impairment.

Surface interactions of C and C(3) polyols with γ-Al2O3 and the role of coadsorbed water.

The formation of surface species from two- and three-carbon polyols on γ-Al(2)O(3) in the presence and absence of coadsorbed water is investigated. Aqueous-phase adsorption isotherms indicate that competitive adsorption between water and polyol inhibits the uptake of the polyol molecules on γ-Al(2)O(3) and that the polyol with the most hydroxyl groups, glycerol, experienced the greatest uptake. Deuterium solid echo pulse NMR measurements support the fact that glycerol strongly interacts with γ-Al(2)O(3) in the presence of physisorbed water and that ethylene glycol interacts with γ-Al(2)O(3) only after the physisorbed water has been removed. In situ high-vacuum FT-IR analysis combined with DFT simulations demonstrate that glycerol readily forms a multidentate alkoxy species through its primary hydroxyl groups with coordinatively unsaturated Al atoms of γ-Al(2)O(3) in the presence of physisorbed water. This surface species exhibits a bridging alkoxy bond from one of its primary hydroxyl groups and a strong interaction with the remaining primary hydroxyl group. FT-IR analysis of 1,3-propanediol on γ-Al(2)O(3) also demonstrates the formation of a multidentate alkoxy species in the presence of coadsorbed water. In contrast, polyols with hydroxyl groups only on the one- and two-carbon atoms, ethylene glycol, and 1,2-propanediol do not form alkoxy bonds with the γ-Al(2)O(3) surface when coadsorbed water is present. These polyols will form alkoxy bonds to γ-Al(2)O(3) when coadsorbed water is removed, and these alkoxy species are removed when water is readsorbed on the sample. The formation of strongly bound, stable multidentate alkoxy species by ethylene glycol and 1,2-propanediol on γ-Al(2)O(3) is prevented by steric limitations of vicinal alcohol groups.

Paranoid symptoms and hallucinations among the older people in Western Europe.

OBJECTIVE: It is not clear whether the prevalence of psychosis increases with age. We studied the age-specific prevalence of psychotic symptoms in older people in Western Europe. METHODS: Older people without dementia (age 65-104 years, N = 8762) from the western part of Europe in the EURODEP concerted action took part in psychiatric examinations. RESULTS: In total, 2.4% of the men and 2.9% of the women had psychotic symptoms. Using a multilevel logistic regression model that included gender and age as a continuous variable, we found that a 5-year increase in age increased the prevalence of psychotic symptoms (odds ratio 1.2 95% confidence interval 1.06-1.3, p = 0.001). A second multilevel regression model showed that wishing to be dead, depressed mood, functional disability, not being married and cognitive impairment measured with Mini mental state examination were all associated with psychotic symptoms whereas gender was not. CONCLUSION: The prevalence of psychotic symptoms in non-demented older people increases with age, and these symptoms are associated with other psychopathology, social isolation and problems with daily living.

Association between environmental tobacco smoke exposure and dementia syndromes.

OBJECTIVES: Environmental tobacco smoke (ETS) has a range of adverse health effects, but its association with dementia remains unclear and with dementia syndromes unknown. We examined the dose-response relationship between ETS exposure and dementia syndromes. METHODS: Using a standard method of GMS, we interviewed 5921 people aged ≥60 years in five provinces in China in 2007-2009 and characterised their ETS exposure. Five levels of dementia syndrome were diagnosed using the Automated Geriatric Examination for Computer Assisted Taxonomy instrument. The relative risk (RR) of moderate (levels 1-2) and severe (levels 3-5) dementia syndromes among participants exposed to ETS was calculated in multivariate adjusted regression models. RESULTS: 626 participants (10.6%) had severe dementia syndromes and 869 (14.7%) moderate syndromes. Participants exposed to ETS had a significantly increased risk of severe syndromes (adjusted RR 1.29, 95% CI 1.05 to 1.59). This was dose-dependently related to exposure level and duration. The cumulative exposure dose data showed an adjusted RR of 0.99 (95% CI 0.76 to 1.28) for >0-24 level years of exposure, 1.15 (95% CI 0.93 to 1.42) for 25-49 level years, 1.18 (95% CI 0.87 to 1.59) for 59-74 level years, 1.39 (95% CI 1.03 to 1.84) for 75-99 level years and 1.95 (95% CI 1.34 to 2.83) for ≥100 level years. Significant associations with severe syndromes were found in never smokers and in former/current smokers. There were no positive associations between ETS and moderate dementia syndromes. CONCLUSIONS: ETS should be considered an important risk factor for severe dementia syndromes. Avoidance of ETS may reduce the rates of severe dementia syndromes worldwide.

Correction: Metastasis Suppressor microRNA-335 Targets the Formin Family of Actin Nucleators.

[This corrects the article DOI: 10.1371/journal.pone.0078428.].