Percolation Behaviour in the Magnetic Permeability and Electrical Conductivity in Conducting Magnetic - Insulating Non Magnetic Binary Composites.

Experimental results of the complex magnetic permeability (µ) and the electrical conductivity (σ) of a granular paramagnetic Gadolinium Gallium Garnet (GGG: 0.3 to 26 Vol. %) and Teflon (PTFE) system are presented, and discussed in relation to previously published (conductivity) and unpublished (permeability) studies on granular Fe3O4 - talc and Ni - talc wax systems. In these systems, plots of the real conductivity ( σ m ' ) against the volume fraction (φ) lie on a characteristic sigmoid curves that when fitted to the Two Exponent Phenomenological Percolation Equation (TEPPE), confirm the existence of "percolation microstructures" with critical volume fractions (φ c). The plots of the real and imaginary permeability ( µ m ' ) and ( µ m ″ ), satisfactorily fit to the TEPPE using the φ c obtained in each case from the "conductivity" measurements. In all three cases, the conductivity results gave the exponent t > 2, and the permeability results gave t < 1.

Sleeping arrangements and mass distribution of bed nets in six districts in central and northern Mozambique.

OBJECTIVE: Universal coverage with insecticide-treated bed nets is a cornerstone of modern malaria control. Mozambique has developed a novel bed net allocation strategy, where the number of bed nets allocated per household is calculated on the basis of household composition and assumptions about who sleeps with whom. We set out to evaluate the performance of the novel allocation strategy. METHODS: A total of 1994 households were visited during household surveys following two universal coverage bed net distribution campaigns in Sofala and Nampula provinces in 2010-2013. Each sleeping space was observed for the presence of a bed net, and the sleeping patterns for each household were recorded. The observed coverage and efficiency were compared to a simulated coverage and efficiency had conventional allocation strategies been used. A composite indicator, the product of coverage and efficiency, was calculated. Observed sleeping patterns were compared with the sleeping pattern assumptions. RESULTS: In households reached by the campaign, 93% (95% CI: 93-94%) of sleeping spaces in Sofala and 84% (82-86%) in Nampula were covered by campaign bed nets. The achieved efficiency was high, with 92% (91-93%) of distributed bed nets in Sofala and 93% (91-95%) in Nampula covering a sleeping space. Using the composite indicator, the novel allocation strategy outperformed all conventional strategies in Sofala and was tied for best in Nampula. The sleeping pattern assumptions were completely satisfied in 66% of households in Sofala and 56% of households in Nampula. The most common violation of the sleeping pattern assumptions was that male children 3-10 years of age tended not to share sleeping spaces with female children 3-10 or 10-16 years of age. CONCLUSIONS: The sleeping pattern assumptions underlying the novel bed net allocation strategy are generally valid, and net allocation using these assumptions can achieve high coverage and compare favourably with conventional allocation strategies.

Occult hepatitis B virus coinfection in HIV-positive African migrants to the UK: a point prevalence study.

OBJECTIVES: Occult (surface antigen-negative/DNA-positive) hepatitis B virus (HBV) infection is common in areas of the world where HBV is endemic. The main objectives of this study were to determine the prevalence of occult HBV infection in HIV-infected African migrants to the UK and to determine factors associated with occult coinfection. METHODS: This anonymized point-prevalence study identified Africans attending three HIV clinics, focussing on patients naïve to antiretroviral therapy (ART). Stored blood samples were tested for HBV DNA. Prevalence was calculated in the entire cohort, as well as in subpopulations. Risk factors for occult HBV coinfection were identified using logistic regression analysis. RESULTS: Among 335 HIV-positive African migrants, the prevalence of occult HBV coinfection was 4.5% [95% confidence interval (CI) 2.8-7.4%] overall, and 6.5% (95% CI 3.9-10.6%) and 0.8% (95% CI 0.2-4.6%) in ART-naïve and ART-experienced patients, respectively. Among ART-naïve anti-HBV core (anti-HBc)-positive patients, the prevalence was 16.4% (95% CI 8.3-25.6%). The strongest predictor of occult coinfection was anti-HBc positivity [odds ratio (OR) 7.4; 95% CI 2.0-27.6]. Median HBV DNA and ALT levels were 54 IU/mL [interquartile range (IQR) 33-513 IU/mL] and 22 U/L (IQR 13-27 U/L), respectively. CONCLUSIONS: Occult HBV coinfection remains under-diagnosed in African HIV-infected patients in the UK. Given the range of HBV DNA levels observed, further studies are warranted to determine its clinical significance and to guide screening strategies and ART selection in these patients.

A markerless motion capture system can reliably determine peak trunk flexion while squatting with and without a weighted vest.

Markerless motion capture has improved physical screening efficiency in sport and occupational settings; however, reliability of kinematic measurements from commercial systems must be established. Further, the impact of torso-borne equipment on these measurements is unclear. The purpose of this study was to evaluate the reliability of HumanTrak, a markerless motion capture system, for estimating peak trunk flexion in squat movements with and without a weighted vest. Eighteen participants completed body weight squats (BWSQ) and overhead squats (OHSQ) to their maximum depth (unrestricted-range) and to a plyometric box (fixed-range) while wearing no body armour (NBA) or 9 kg body armour (BA9). Peak trunk flexion was measured using HumanTrak. Testing was performed in two sessions on one day (intra-day) and one session on a separate day (inter-day) to assess reliability. HumanTrak had a standard error of measurement < 3.74° across all movements and conditions. Reliability was good to excellent (ICC = 0.82-0.96) with very large to nearly perfect Pearson correlations (r > 0.80) for all comparisons except unrestricted-range BWSQ with BA9 (ICC = 0.60-0.71, r = 0.71). HumanTrak was more reliable for intra- than inter-day, but reliability was still excellent for almost all inter-day comparisons (ICC > 0.82). HumanTrak is reliable for detecting differences in peak trunk flexion > 8.5° when body armour is not worn and > 10.5° when body armour is worn. Practitioners can assess meaningful changes in sagittal plane trunk motion when screening squat movements regardless of whether body armour is worn.

Using extended reality (XR) for medical training and real-time clinical support during deep space missions.

Medical events can affect space crew health and compromise the success of deep space missions. To successfully manage such events, crew members must be sufficiently prepared to manage certain medical conditions for which they are not technically trained. Extended Reality (XR) can provide an immersive, realistic user experience that, when integrated with augmented clinical tools (ACT), can improve training outcomes and provide real-time guidance during non-routine tasks, diagnostic, and therapeutic procedures. The goal of this study was to develop a framework to guide XR platform development using astronaut medical training and guidance as the domain for illustration. We conducted a mixed-methods study-using video conference meetings (45 subject-matter experts), Delphi panel surveys, and a web-based card sorting application-to develop a standard taxonomy of essential XR capabilities. We augmented this by identifying additional models and taxonomies from related fields. Together, this "taxonomy of taxonomies," and the essential XR capabilities identified, serve as an initial framework to structure the development of XR-based medical training and guidance for use during deep space exploration missions. We provide a schematic approach, illustrated with a use case, for how this framework and materials generated through this study might be employed.

Multicentre survey of radiologically inserted gastrostomy feeding tube (RIG) in the UK.

AIMS: To evaluate the variance in current UK clinical practice and clinical outcomes for direct percutaneous radiologically inserted gastrostomy (RIG). MATERIALS AND METHODS: A prospective UK multicentre survey of RIG performed between October 2008 and August 2010 was performed through the British Society of Gastrointestinal and Abdominal Radiology (BSGAR). RESULTS: Data from 684 patients were provided by 45 radiologists working at 17 UK centres. Two hundred and sixty-three cases (40%) were performed with loop-retained catheters, and 346 (53%) with balloon-retained devices. Sixty percent of all patients experienced pain in the first 24 h, but settled in the majority thereafter. Early complications, defined as occurring in the first 24 h, included minor bleeding (1%), wound infection (3%), peritonism (2%), and tube misplacement (1%). Late complications, defined as occurring between day 2 and day 30 post-procedure, included mild pain (30%), persisting peritonism (2%), and 30 day mortality of 1% (5/665). Pre-procedural antibiotics or anti-methicillin-resistant Staphylococcus aureus (MRSA) prophylaxis did not affect the rate of wound infection, peritonitis, post-procedural pain, or mortality. Ninety-three percent of cases were performed using gastropexy. Gastropexy decreased post-procedural pain (p < 0.001), but gastropexy-related complications occurred in 5% of patients. However, post-procedure pain increased with the number of gastropexy sutures used (p < 0.001). The use of gastropexy did not affect the overall complication rate or mortality. Post-procedure pain increased significantly as tube size increased (p < 0.001). The use of balloon-retention feeding tubes was associated with more pain than the deployment of loop-retention devices (p < 0.001). CONCLUSION: RIG is a relatively safe procedure with a mortality of 1%, with or without gastropexy. Pain is the commonest complication. The use of gastropexy, fixation dressing or skin sutures, smaller tube sizes, and loop-retention catheters significantly reduced the incidence of pain. There was a gastropexy-related complication rate in 5% of patients. Neither pre-procedural antibiotics nor anti-MRSA prophylaxis affected the rate of wound infection.

An anterior cruciate ligament injury prevention framework: incorporating the recent evidence.

Anterior cruciate ligament (ACL) injury rates have increased by ∼50% over the last 10 years. These figures suggest that ACL focused research has not been effective in reducing injury rates among community level athletes. Training protocols designed to reduce ACL injury rates have been both effective (n = 3) and ineffective (n = 7). Although a rationale for the use of exercise to reduce ACL injuries is established, the mechanisms by which they act are relatively unknown. This article provides an injury prevention framework specific to noncontact ACL injuries and the design of prophylactic training protocols. It is also apparent that feedback within this framework is needed to determine how biomechanically relevant risk factors like peak joint loading and muscular support are influenced following training. It is by identifying these links that more effective ACL injury prevention training programs can be developed, and, in turn, lead to reduced ACL injury rates in the future.

Semi-Empirical Astronomical Light Pollution Evaluation of Satellite Constellations.

Several commercial organizations have recently launched or plan to launch constellations containing thousands of satellites. Such large constellations potentially adversely affect astronomical observations. This study formulates a set of indicators that assess the impact of light pollution from different constellations on ground-based visible band astronomy. These include the statistically expected number of visible and sunlit satellites above ground-based observers, as well as the number that are also expected to be brighter than the currently recommended limit for constellation satellites. The latter indicator provides a consolidated means to evaluate the potential for a constellation to affect ground-based astronomy too severely, by simultaneously accounting for the effects of constellation population, orbital distribution as well as brightness magnitude and variability. For existing constellations, the evaluation process incorporates actual satellite photometric brightness measurements, which are becoming increasingly available in web-accessible databases and repositories. For proposed constellations, a semi-empirical method allows rough approximations of pre-launch light pollution levels, based on observed brightness distributions observed of currently orbiting analog satellites.

A general swimming response in exhausted obligate swimming fish.

Marine organisms normally swim at elevated speeds relative to cruising speeds only during strenuous activity, such as predation or escape. We measured swimming speeds of 29 ram ventilating sharks from 10 species and of three Atlantic bluefin tunas immediately after exhaustive exercise (fighting a capture by hook-and-line) and unexpectedly found all individuals exhibited a uniform mechanical response, with swimming speed initially two times higher than the cruising speeds reached approximately 6 h later. We hypothesized that elevated swimming behaviour is a means to increase energetic demand and drive the removal of lactate accumulated during capture via oxidation. To explore this hypothesis, we estimated the mechanical work that must have been spent by an animal to elevate its swim speed and then showed that the amount of lactate that could have been oxidized to fuel it comprises a significant portion of the amount of lactate normally observed in fishes after exhaustive exercise. An estimate for the full energetic cost of the catch-and-release event ensued.

Modulating progenitor accumulation attenuates lung angiogenesis in a mouse model of asthma.

Asthmatic responses are associated with the lung homing of bone marrow (BM)-derived progenitors implicated as effectors of disease pathology. Studies have shown that increases in lung extracted vascular endothelial progenitor cells (VEPCs) correlate with airway angiogenesis and declining lung function. We investigated the effect of modulating lung homing of VEPCs on tissue remodelling and airway hyperresponsiveness (AHR). BALB/c mice were sensitised to ovalbumin, subjected to a chronic exposure protocol and given early concurrent or delayed treatment with a modulator of progenitor traffic, AMD3100 (CXC chemokine receptor 4 antagonist; inhibits chemotactic activity of stromal-derived factor-1α on VEPCs). After ovalbumin challenge, early haemopoietic stem cells (HSCs) and VEPCs were enumerated along with indices of airway inflammation, lung morphometry and AHR. Following ovalbumin challenge, there was a decrease in BM and an associated increase in the lung tissue-extracted HSCs and VEPCs, together with increases in airway eosinophilia, microvessel density and AHR. These outcomes were significantly inhibited by early concurrent treatment with AMD3100. Where lung disease was established, delayed treatment with AMD3100 significantly attenuated HSC numbers and lung angiogenesis but only partially reversed sustained AHR compared with untreated ovalbumin-exposed mice. Progenitor lung homing is associated with the development of asthma pathology, and early modulation of this accumulation can prevent airway remodelling and lung dysfunction.

Low secondary transmission of 2009 pandemic influenza A (H1N1) in households following an outbreak at a summer camp: relationship to timing of exposure.

Following an outbreak of 2009 pandemic influenza A (H1N1) at a residential summer camp for boys aged 10-16 years, we assessed secondary household transmission of the novel virus after their return home. Of 212 study participants who attended camp, 49 had confirmed or probable influenza for a primary attack rate of 23%. Of 87 exposed household contacts who did not attend camp, only three instances of probable transmission were observed, for a household secondary attack rate of 3·5%. All secondary cases occurred in households where the ill camp attendee returned home 1 day after onset of illness, with an attack rate of 14·3% in household contacts in this category. Returning home after peak infectivity to others and advanced warning prior to reintegration of sick individuals into the household probably contributed to the overall low secondary attack rate observed.

The acute and long-term effects of Middle East sand particles on the rat airway following a single intratracheal instillation.

Military personnel deployed in the Middle East have emphasized concerns regarding high levels of dust generated from blowing desert sand and the movement of troops and equipment. Airborne particulate matter levels (PM(10); PM < 10 µm) in the region may exceed 1500 µg/m(3), significantly higher than the military exposure guideline (MEG) of 50 µg/m(3). Increases in PM(10) have been linked to a rise in incidences of asthma, obstructive pulmonary disease, lung cancer, and cardiovascular diseases. Male Sprague-Dawley rats received a single intratracheal (IT) instillation of 1, 5, or 10 mg of Middle East PM(10) collected at a military occupied site in Kuwait, silica (positive control), or titanium dioxide (TiO(2); negative control) suspended in 400 µl sterile saline, or saline alone (vehicle control). Twenty-four hours, 3 d, 7 d and 6 mo postexposure (n = 15/group), organs including lung were evaluated for histopathological changes and for particle contaminants. Bronchoalveolar fluid (BALF) was also analyzed for cellular and biochemical parameters, including cytokines and chemokines. Instillation of silica resulted in early, pronounced, sustained inflammation indicated by significant increases in levels of total protein and neutrophils, and activities of lactate dehydrogenase activity and ß-glucuronidase activity. Lower magnitude and transient changes using the same markers were observed in animals exposed to TiO(2) and Middle East PM(10). The results suggest that for acute exposures, this Middle East PM(10) is a nuisance-type dust with relatively low toxicity. However, since average deployment of military personnel to the Middle East is 180 d with potential for multiple follow-on tours, chronic exposure studies are needed to fully understand the pulmonary effects associated with Middle East PM exposure.

Computed tomography osteoabsorptiometry-based investigation on subchondral bone plate alterations in sacroiliac joint dysfunction.

Sacroiliac joint dysfunction (SIJD) is an underappreciated source of back pain. Mineralization patterns of the sacroiliac (SIJ) subchondral bone plate (SCB) may reflect long-term adaptations to the loading of the joint. Mineralization densitograms of 27 SIJD patients and 39 controls, were obtained using CT osteoabsorptiometry. Hounsfield unit (HU) values of the SCB mineralization of superior, anterior and inferior regions on the iliac and sacral auricular surfaces were derived and statistically compared between SIJD-affected and control cohorts. Healthy controls showed higher HU values in the iliac; 868 ± 211 (superior), 825 ± 121 (anterior), 509 ± 114 (inferior), than in the sacral side; 541 ± 136 (superior), 618 ± 159 (anterior), 447 ± 91 (inferior), of all regions (p < 0.01). This was similar in SIJD; ilium 908 ± 170 (superior), 799 ± 166 (anterior), 560 ± 135 (inferior), sacrum 518 ± 150 (superior), 667 ± 151 (anterior), 524 ± 94 (inferior). In SIJD, no significant HU differences were found when comparing inferior sacral and iliac regions. Furthermore, HU values in the inferior sacral region were significantly higher when compared to the same region of the healthy controls (524 ± 94 vs. 447 ± 91, p < 0.01). Region mineralization correlated negatively with age (p < 0.01). SIJD-affected joints reflect a high mineralization of the sacral inferior region, suggesting increased SIJD-related mechanical stresses. Age-related SCB demineralization is present in all individuals, regardless of dysfunction.

Angiogenic effects despite limited cell survival of bone marrow-derived mesenchymal stem cells under ischemia.

Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent and secrete angiogenic factors, which could help patients with occlusive arterial diseases. We hypothesize that MSCs, in comparison to fibroblasts, survive better under hypoxic conditions in vitro and in vivo. MSCs and fibroblasts from L2G mice expressing firefly luciferase and GFP were cultured in normoxic and hypoxic conditions for 24 hours. In vitro cell viability was tested by detecting apoptosis and necrosis. MSCs released higher amounts of VEGF (281.1 +/- 62.6 pg/ml) under hypoxic conditions compared to normoxia (154.9 +/- 52.3 pg/ml, p = NS), but were less tolerant to hypoxia (45 +/- 7.9%) than fibroblasts (28.1 +/- 3.6%, p = NS). A hindlimb ischemia model was created by ligating the femoral artery of 18 FVB mice. After one week, 1 x 106 cells (MSCs, fibroblasts or saline) were injected into the limb muscles of each animal (n = 6 per group). Bioluminescence measurement to assess the viability of luciferase positive cells showed significant proliferation of MSCs on day four compared to fibroblasts (p = 0.001). Three weeks after cell delivery, the capillary to muscle fiber ratio of ischemic areas was analyzed. In the MSC group, vessel density was significantly higher than in the fibroblast or control group (0.5 +/- 0.08 and 0.3 +/- 0.03). Under hypoxia, MSCs produced more VEGF compared to normal conditions and MSC transplantation into murine ischemic limbs led to an increase in vessel density, although MSC survival was limited. This study suggests that MSC transplantation may be an effective and clinically relevant tool in the therapy of occlusive arterial diseases.

siRNA silencing of keratinocyte-specific GFP expression in a transgenic mouse skin model.

Small interfering RNAs (siRNAs) can be designed to specifically and potently target and silence a mutant allele, with little or no effect on the corresponding wild-type allele expression, presenting an opportunity for therapeutic intervention. Although several siRNAs have entered clinical trials, the development of siRNA therapeutics as a new drug class will require the development of improved delivery technologies. In this study, a reporter mouse model (transgenic click beetle luciferase/humanized monster green fluorescent protein) was developed to enable the study of siRNA delivery to skin; in this transgenic mouse, green fluorescent protein reporter gene expression is confined to the epidermis. Intradermal injection of siRNAs targeting the reporter gene resulted in marked reduction of green fluorescent protein expression in the localized treatment areas as measured by histology, real-time quantitative polymerase chain reaction and intravital imaging using a dual-axes confocal fluorescence microscope. These results indicate that this transgenic mouse skin model, coupled with in vivo imaging, will be useful for development of efficient and 'patient-friendly' siRNA delivery techniques and should facilitate the translation of siRNA-based therapeutics to the clinic for treatment of skin disorders.

Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan.

Our objective is to assess treatment efficacy, safety and pattern of response and recurrence in patients with recurrent high-grade glioma treated with bevacizumab and irinotecan. We reviewed retrospectively 51 patients with recurrent high-grade glioma treated with this combination at the Henry Ford Hermelin Brain Tumor Center from 11/15/2005 to 04/01/2008. The 6-month progression-free survival (PFS) for anaplastic gliomas (AGs) was 78.6 and 63.7% for glioblastoma. The median PFS was 13.4 months for AG and 7.6 months for those with glioblastoma. The overall survival rate (OS) at 6 months was 85.7% for AG and 78.0% for glioblastoma. The 12-month OS was 77.9% for AG and 42.6% for glioblastoma. The median OS time for AGs was not reached and was 11.5 months for those with glioblastoma. Thirty-six out of 51 (70.59%) patients demonstrated partial (32/51) or complete (4/51) radiographic response to treatment and 8/51 (15.69%) remained stable. Of the 38 who demonstrated progression on post-gadolinium studies, 23 showed distant progression with or without local recurrence. Seven patients showed progression on FLAIR without concordant findings on post-Gd sequences. Six patients (11.76%) discontinued treatment due to a treatment-emergent adverse event, including one with end-stage renal failure and another with gastric perforation. No symptomatic intracranial hemorrhages were reported. Patients with recurrent high-grade glioma treated with bevacizumab plus irinotecan demonstrate an excellent radiographic response rate and improved clinical outcome when compared to historical data. The high rate of distant tumor progression suggests that tumors may adapt to inhibition of angiogenesis by increased infiltration and vascular co-option.

Functional characterization of AC5 gain-of-function variants: Impact on the molecular basis of ADCY5-related dyskinesia.

Adenylyl cyclases are key points for the integration of stimulatory and inhibitory G protein-coupled receptor (GPCR) signals. Adenylyl cyclase type 5 (AC5) is highly expressed in striatal medium spiny neurons (MSNs), and is known to play an important role in mediating striatal dopaminergic signaling. Dopaminergic signaling from the D1 expressing MSNs of the direct pathway, as well as the D2 expressing MSNs of the indirect pathway both function through the regulation of AC5 activity, controlling the production of the 2nd messenger cAMP, and subsequently the downstream effectors. Here, we used a newly developed cell line that used Crispr-Cas9 to eliminate the predominant adenylyl cyclase isoforms to more accurately characterize a series of AC5 gain-of-function mutations which have been identified in ADCY5-related dyskinesias. Our results demonstrate that these AC5 mutants exhibit enhanced activity to Gαs-mediated stimulation in both cell and membrane-based assays. We further show that the increased cAMP response at the membrane effectively translates into increased downstream gene transcription in a neuronal model. Subsequent analysis of inhibitory pathways show that the AC5 mutants exhibit significantly reduced inhibition following D2 dopamine receptor activation. Finally, we demonstrate that an adenylyl cyclase "P-site" inhibitor, SQ22536 may represent an effective future therapeutic mechanism by preferentially inhibiting the overactive AC5 gain-of-function mutants.

A Review of Magnetic Particle Imaging and Perspectives on Neuroimaging.

Magnetic particle imaging is an emerging tomographic technique with the potential for simultaneous high-resolution, high-sensitivity, and real-time imaging. Magnetic particle imaging is based on the unique behavior of superparamagnetic iron oxide nanoparticles modeled by the Langevin theory, with the ability to track and quantify nanoparticle concentrations without tissue background noise. It is a promising new imaging technique for multiple applications, including vascular and perfusion imaging, oncology imaging, cell tracking, inflammation imaging, and trauma imaging. In particular, many neuroimaging applications may be enabled and enhanced with magnetic particle imaging. In this review, we will provide an overview of magnetic particle imaging principles and implementation, current applications, promising neuroimaging applications, and practical considerations.

Functional characterization of novel presenilin-2 variants identified in human breast cancers.

We identified in breast cancer cases two germline alterations, R62H and R71W, in presenilin-2 (PS-2), a gene involved in familial Alzheimer's disease (FAD). The role of these alleles in FAD is unclear, but neither allele affected Abeta(42)/Abeta(40) ratio. However, both R62H and R71W alterations compromised PS-2 function in Notch signaling in Caenorhabditis elegans and cell growth inhibition in mouse embryonic fibroblasts, and these effects were dependent on gene dosage. We found that both alterations enhanced the degradation of the PS-2 full-length protein, indicating that they may have a loss-of function effect. The effect of the R71W alteration was noticeably stronger, and we observed an almost threefold higher frequency of this allele in breast cancer cases versus controls, but this difference did not reach statistical significance. Nonetheless, these results collectively suggest that the novel PS-2 alleles described here, especially R71W, affect PS-2 function and may potentially confer a moderate risk of susceptibility to breast cancer.

Multiple functions for actin during filamentous growth of Saccharomyces cerevisiae.

Saccharomyces cerevisiae is dimorphic and switches from a yeast form to a pseudohyphal (PH) form when starved for nitrogen. PH cells are elongated, bud in a unipolar manner, and invade the agar substrate. We assessed the requirements for actin in mediating the dramatic morphogenetic events that accompany the transition to PH growth. Twelve "alanine scan" alleles of the single yeast actin gene (ACT1) were tested for effects on filamentation, unipolar budding, agar invasion, and cell elongation. Some act1 mutations affect all phenotypes, whereas others affect only one or two aspects of PH growth. Tests of intragenic complementation among specific act1 mutations support the phenotypic evidence for multiple actin functions in filamentous growth. We present evidence that interaction between actin and the actin-binding protein fimbrin is important for PH growth and suggest that association of different actin-binding proteins with actin mediates the multiple functions of actin in filamentous growth. Furthermore, characterization of cytoskeletal structure in wild type and act1/act1 mutants indicates that PH cell morphogenesis requires the maintenance of a highly polarized actin cytoskeleton. Collectively, this work demonstrates that actin plays a central role in fungal dimorphism.