Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection

Human Immunodeficiency Virus (HIV) is a retrovirus that can result in rare opportunistic infections occurring in humans. The onset of these infections is known as Acquired Immune Deficiency Syndrome (AIDS). Sexual transmission is responsible for the majority of infections 1, resulting in transmission of HIV due to infected semen or vaginal and cervical secretions containing infected lymphocytes. HIV microbicides are formulations of chemical or biological agents that can be applied to the vagina or rectum with the intention of reducing the acquisition of HIV. Tenofovir is an NRTI that is phosphorylated by adenylate kinase to tenofovir diphosphate, which in turn competes with deoxyadeosine 5’-triphosphate for incorporation into newly synthesized HIV DNA. Once incorporated, tenofovir diphosphate results in chain termination, thus inhibiting viral replication. Tenofovir has been formulated into a range of vaginal formulations, such as rings, tablets gels and films. It has been shown to safe and effective in numerous animal models, while demonstrating safety and acceptability in numerous human trials. The most encouraging results came from the CAPRISA 004 clinical trial which demonstrated that a 1% Tenofovir vaginal gel reduced HIV infection by approximately 39%.

BRCA1, FANCD2 and Chk1 are potential molecular targets for the modulation of a radiation-induced DNA damage response in bystander cells

Radiotherapy is an important treatment option for many human cancers. Current research is investigating the use of molecular targeted drugs in order to improve responses to radiotherapy in various cancers. The cellular response to irradiation is driven by both direct DNA damage in the targeted cell and intercellular signalling leading to a broad range of bystander effects. This study aims to elucidate radiation-induced DNA damage response signalling in bystander cells and to identify potential molecular targets to modulate the radiation induced bystander response in a therapeutic setting. Stalled replication forks in T98G bystander cells were visualised via bromodeoxyuridine (BrdU) nuclear foci detection at sites of single stranded DNA. γH2AX co-localised with these BrdU foci. BRCA1 and FANCD2 foci formed in T98G bystander cells. Using ATR mutant F02-98 hTERT and ATM deficient GM05849 fibroblasts it could be shown that ATR but not ATM was required for the recruitment of FANCD2 to sites of replication associated DNA damage in bystander cells whereas BRCA1 bystander foci were ATM-dependent. Phospho-Chk1 foci formation was observed in T98G bystander cells. Clonogenic survival assays showed moderate radiosensitisation of directly irradiated cells by the Chk1 inhibitor UCN-01 but increased radioresistance of bystander cells. This study identifies BRCA1, FANCD2 and Chk1 as potential targets for the modulation of radiation response in bystander cells. It adds to our understanding of the key molecular events propagating out-of-field effects of radiation and provides a rationale for the development of novel molecular targeted drugs for radiotherapy optimisation.

Susceptibility to Invasive Meningococcal Disease: Polymorphism of Complement System Genes and Neisseria meningitidis Factor H Binding Protein

BACKGROUND: Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH) is associated with altered risk of invasive meningococcal disease (IMD). We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP) affected the risk association.

METHODS: We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.

RESULTS: Rs12085435 A in C8B was associated with odds ratio (OR) of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction). A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10-4). There was no bacterial load (CtrA cycle threshold) difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025).

DISCUSSION: The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become important.

Cross-age tutoring in kindergarten and elementary school settings: a systmeatic review and meta-analysis

Background: Qualified teaching staffs are neither available nor affordable to provide large numbers of children with individual attention. One solution to providing individual tuition has been the development of tutoring programs that are delivered by nonprofessional tutors, such as classmates, older children and community volunteers. Objectives: We have conducted a systematic review of cross-age tutoring interventions delivered by non-professional tutors to children between 5 and 11 years old. Only randomized controlled trials with reliable measures of academic outcomes, and continuing for at least 12 weeks, compared to instruction as usual, were included. Results: Searches of electronic databases and previous reviews, and contacts with researchers yielded 11,564 titles; after screening, 15 studies were included in the analysis. Cross-age tutoring showed small significant effects for tutees on the composite measure of reading (g=0.18, 95% CI: 0.08, 0.27, N=8251), decoding skills (g=0.29, 95% CI: 0.13, 0.44, N=7081), and reading comprehension (g=0.11, 95% CI: 0.01, 0.21, N=6945). No significant effects were detected for other reading sub-skills or for mathematics. The quality of evidence is decreased by study limitations and high heterogeneity of effects. Conclusions: The benefits for tutees of non-professional peer and cross-age tutoring can be given a positive but weak recommendation, considering the low quality of evidence and lack of cost information. Subgroup analyses suggested that highly-structured reading programs may be more useful than loosely-structured programs. Large-scale replication trials using factorial design, process evaluations, reliable outcome measures and logic models are needed to better understand under what conditions, and for whom, cross-age non-professional tutoring may be effective.

Cross-age tutoring in kindergarten and elementary school settings: A systematic review and meta-analysis

This systematic review summarizes effects of peer tutoring delivered to children between 5 and 11 years old by non-professional tutors, such as classmates, older children and adult community peer volunteers. Inclusion criteria for the review included tutoring studies with a randomized controlled trial design, reliable measures of academic outcomes, and duration of at least 12 weeks. Searches of electronic databases, previous reviews, and contacts with researchers yielded 11,564 titles. After screening, 15 studies were included in the analysis. Cross-age tutoring showed small significant effects for tutees on the composite measure of reading (g = 0.18, 95% CI: 0.08, 0.27, N = 8251), decoding skills (g = 0.29, 95% CI: 0.13, 0.44, N = 7081), and reading comprehension (g = 0.11, 95% CI: 0.01, 0.21, N = 6945). No significant effects were detected for other reading sub-skills or for mathematics. The benefits to tutees of non-professional cross-age peer tutoring can be given a positive, but weak recommendation. Effect Sizes were modest and in the range −0.02 to 0.29. Questions regarding study limitations, lack of cost information, heterogeneity of effects, and the relatively small number of studies that have used a randomized controlled trial design means that the evidence base is not as strong as it could be. Subgroup analyses of included studies indicated that highly-structured reading programmes were of more benefit than those that were loosely-structured. Large-scale replication trials using factorial designs, reliable outcome measures, process evaluations and logic models are needed to better understand under what conditions, and for whom, cross-age non-professional peer tutoring may be most effective.

Replication of the association of GLT6D1 with aggressive periodontitis in a Sudanese population

BACKGROUND: Susceptibility to aggressive periodontitis (AgP) is influenced by genetic as well as environmental factors. Studies linking gene variants to AgP have been mainly centred in developed countries with limited data from Africa.
AIM: To investigate whether previously reported candidate gene associations with AgP could be replicated in a population from Sudan.


METHODS: The investigation was a case-control design. Cases with AgP (n = 132) and controls (n = 136) were identified from patients attending the Periodontal Department in Khartoum Dental Hospital. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Analysis focused on gene variants with a minor allele frequency (MAF) > 25% in the Sudanese subjects that had previously been reported to be associated with AgP.


RESULTS: One candidate gene rs1537415 (GLT6D1) was significantly associated with AgP, OR = 1.50 (95% CI 1.04-2.17), p = 0.0295 (increasing to p = 0.09 after correction for multiple testing). The association strengthened to OR = 1.56 (95% CI 1.15-2.16), p = 0.0042 when the controls were supplemented with data from the Hap map for the Yoruba in Ibadan (n = 147) and remained significant (p = 0.013) after correction for multiple testing.


CONCLUSION: The study independently replicated the finding that rs1537415, a variant in glycosyl transferase gene GLT6D1, is associated with AgP and provided the first report of genetic associations with AgP in a Sudanese population.

Recombinant Subgroup B Human Respiratory Syncytial Virus Expressing Enhanced Green Fluorescent Protein Efficiently Replicates in Primary Human Cells and Is Virulent in Cotton Rats

Human respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro and in vivo models of HRSV focus almost exclusively on subgroup A viruses. Here, a recombinant (r) subgroup B virus (rHRSV(B05)) was generated based on a consensus genome sequence obtained directly from an unpassaged clinical specimen from a hospitalized infant. An additional transcription unit containing the gene encoding enhanced green fluorescent protein (EGFP) was introduced between the phosphoprotein and matrix genes (position 5) of the genome to generate rHRSV(B05)EGFP(5). The recombinant viruses replicated efficiently in both HEp-2 cells and in well-differentiated normal human bronchial cells grown at air-liquid interface. Intranasal infection of cotton rats (Sigmodon hispidus) resulted in high numbers of EGFP(+) cells in epithelia of the nasal septum and conchae. When administered in a relatively large inoculum volume, the virus also replicated efficiently in bronchiolar epithelial cells and spread extensively in both the upper and lower respiratory tracts. Virus replication was not observed in ciliated epithelial cells of the trachea. This is the first virulent rHRSV strain with the genetic composition of a currently circulating wild-type virus. In vivo tracking of infected cells by means of EGFP fluorescence in the absence of cytopathic changes increases the sensitivity of virus detection in HRSV pathogenesis studies.

IMPORTANCE

Virology as a discipline has depended on monitoring cytopathic effects following virus culture in vitro. However, wild-type viruses isolated from patients often do not cause significant changes to infected cells, necessitating blind passage. This can lead to genetic and phenotypic changes and the generation of high-titer, laboratory-adapted viruses with diminished virulence in animal models of disease. To address this, we determined the genome sequence of an unpassaged human respiratory syncytial virus from a sample obtained directly from an infected infant, assembled a molecular clone, and recovered a wild-type recombinant virus. Addition of a gene encoding enhanced green fluorescent protein allowed this wild-type virus to be tracked in primary human cells and living animals in the absence of significant cytopathic effects. Imaging of fluorescent cells proved to be a highly valuable tool for monitoring the spread of virus and may help improve assays for evaluating novel intervention strategies.

Generation of replication-proficient influenza virus NS1 point mutants with interferon-hyperinducer phenotype

The NS1 protein of influenza A viruses is the dedicated viral interferon (IFN)-antagonist. Viruses lacking NS1 protein expression cannot multiply in normal cells but are viable in cells deficient in their ability to produce or respond to IFN. Here we report an unbiased mutagenesis approach to identify positions in the influenza A NS1 protein that modulate the IFN response upon infection. A random library of virus ribonucleoproteins containing circa 40 000 point mutants in NS1 were transferred to infectious virus and amplified in MDCK cells unable to respond to interferon. Viruses that activated the interferon (IFN) response were subsequently selected by their ability to induce expression of green-fluorescent protein (GFP) following infection of A549 cells bearing an IFN promoter-dependent GFP gene. Using this approach we isolated individual mutant viruses that replicate to high titers in IFN-compromised cells but, compared to wild type viruses, induced higher levels of IFN in IFN-competent cells and had a reduced capacity to counteract exogenous IFN. Most of these viruses contained not previously reported NS1 mutations within either the RNA-binding domain, the effector domain or the linker region between them. These results indicate that subtle alterations in NS1 can reduce its effectiveness as an IFN antagonist without affecting the intrinsic capacity of the virus to multiply. The general approach reported here may facilitate the generation of replication-proficient, IFN-inducing virus mutants, that potentially could be developed as attenuated vaccines against a variety of viruses.

How Video Lecture Capture affects Student Engagement in a University Computer Programming Course: Attendance, Video Viewing Behaviours and Student Attitudes

Introduction
The use of video capture of lectures in Higher Education is not a recent occurrence with web based learning technologies including digital recording of live lectures becoming increasing commonly offered by universities throughout the world (Holliman and Scanlon, 2004). However in the past decade the increase in technical infrastructural provision including the availability of high speed broadband has increased the potential and use of videoed lecture capture. This had led to a variety of lecture capture formats including pod casting, live streaming or delayed broadcasting of whole or part of lectures.
Additionally in the past five years there has been a significant increase in the popularity of online learning, specifically via Massive Open Online Courses (MOOCs) (Vardi, 2014). One of the key aspects of MOOCs is the simulated recording of lecture like activities. There has been and continues to be much debate on the consequences of the popularity of MOOCs, especially in relation to its potential uses within established University programmes.
There have been a number of studies dedicated to the effects of videoing lectures.
The clustered areas of research in video lecture capture have the following main themes:
• Staff perceptions including attendance, performance of students and staff workload
• Reinforcement versus replacement of lectures
• Improved flexibility of learning
• Facilitating engaging and effective learning experiences
• Student usage, perception and satisfaction
• Facilitating students learning at their own pace
Most of the body of the research has concentrated on student and faculty perceptions, including academic achievement, student attendance and engagement (Johnston et al, 2012).
Generally the research has been positive in review of the benefits of lecture capture for both students and faculty. This perception coupled with technical infrastructure improvements and student demand may well mean that the use of video lecture capture will continue to increase in frequency in the next number of years in tertiary education. However there is a relatively limited amount of research in the effects of lecture capture specifically in the area of computer programming with Watkins 2007 being one of few studies . Video delivery of programming solutions is particularly useful for enabling a lecturer to illustrate the complex decision making processes and iterative nature of the actual code development process (Watkins et al 2007). As such research in this area would appear to be particularly appropriate to help inform debate and future decisions made by policy makers.
Research questions and objectives
The purpose of the research was to investigate how a series of lecture captures (in which the audio of lectures and video of on-screen projected content were recorded) impacted on the delivery and learning of a programme of study in an MSc Software Development course in Queen’s University, Belfast, Northern Ireland. The MSc is conversion programme, intended to take graduates from non-computing primary degrees and upskill them in this area. The research specifically targeted the Java programming module within the course. It also analyses and reports on the empirical data from attendances and various video viewing statistics. In addition, qualitative data was collected from staff and student feedback to help contextualise the quantitative results.
Methodology, Methods and Research Instruments Used
The study was conducted with a cohort of 85 post graduate students taking a compulsory module in Java programming in the first semester of a one year MSc in Software Development. A pre-course survey of students found that 58% preferred to have available videos of “key moments” of lectures rather than whole lectures. A large scale study carried out by Guo concluded that “shorter videos are much more engaging” (Guo 2013). Of concern was the potential for low audience retention for videos of whole lectures.
The lecturers recorded snippets of the lecture directly before or after the actual physical delivery of the lecture, in a quiet environment and then upload the video directly to a closed YouTube channel. These snippets generally concentrated on significant parts of the theory followed by theory related coding demonstration activities and were faithful in replication of the face to face lecture. Generally each lecture was supported by two to three videos of durations ranging from 20 – 30 minutes.
Attendance
The MSc programme has several attendance based modules of which Java Programming was one element. In order to assess the consequence on attendance for the Programming module a control was established. The control used was a Database module which is taken by the same students and runs in the same semester.
Access engagement
The videos were hosted on a closed YouTube channel made available only to the students in the class. The channel had enabled analytics which reported on the following areas for all and for each individual video; views (hits), audience retention, viewing devices / operating systems used and minutes watched.
Student attitudes
Three surveys were taken in regard to investigating student attitudes towards the videoing of lectures. The first was before the start of the programming module, then at the mid-point and subsequently after the programme was complete.
The questions in the first survey were targeted at eliciting student attitudes towards lecture capture before they had experienced it in the programme. The midpoint survey gathered data in relation to how the students were individually using the system up to that point. This included feedback on how many videos an individual had watched, viewing duration, primary reasons for watching and the result on attendance, in addition to probing for comments or suggestions. The final survey on course completion contained questions similar to the midpoint survey but in summative view of the whole video programme.
Conclusions and Outcomes
The study confirmed findings of other such investigations illustrating that there is little or no effect on attendance at lectures. The use of the videos appears to help promote continual learning but they are particularly accessed by students at assessment periods. Students respond positively to the ability to access lectures digitally, as a means of reinforcing learning experiences rather than replacing them. Feedback from students was overwhelmingly positive indicating that the videos benefited their learning. Also there are significant benefits to part recording of lectures rather than recording whole lectures. The behaviour viewing trends analytics suggest that despite the increase in the popularity of online learning via MOOCs and the promotion of video learning on mobile devices in fact in this study the vast majority of students accessed the online videos at home on laptops or desktops However, in part, this is likely due to the nature of the taught subject, that being programming.
The research involved prerecording the lecture in smaller timed units and then uploading for distribution to counteract existing quality issues with recording entire live lectures. However the advancement and consequential improvement in quality of in situ lecture capture equipment may well help negate the need to record elsewhere. The research has also highlighted an area of potentially very significant use for performance analysis and improvement that could have major implications for the quality of teaching. A study of the analytics of the viewings of the videos could well provide a quick response formative feedback mechanism for the lecturer. If a videoed lecture either recorded live or later is a true reflection of the face to face lecture an analysis of the viewing patterns for the video may well reveal trends that correspond with the live delivery.

RIP kinases: key decision makers in cell death and innate immunity

Innate immunity represents the first line of defence against invading pathogens. It consists of an initial inflammatory response that recruits white blood cells to the site of infection in an effort to destroy and eliminate the pathogen. Some pathogens replicate within host cells, and cell death by apoptosis is an important effector mechanism to remove the replication niche for such microbes. However, some microbes have evolved evasive strategies to block apoptosis, and in these cases host cells may employ further countermeasures, including an inflammatory form of cell death know as necroptosis. This review aims to highlight the importance of the RIP kinase family in controlling these various defence strategies. RIP1 is initially discussed as a key component of death receptor signalling and in the context of dictating whether a cell triggers a pathway of pro-inflammatory gene expression or cell death by apoptosis. The molecular and functional interplay of RIP1 and RIP3 is described, especially with respect to mediating necroptosis and as key mediators of inflammation. The function of RIP2, with particular emphasis on its role in NOD signalling, is also explored. Special attention is given to emphasizing the physiological and pathophysiological contexts for these various functions of RIP kinases.

DNA mismatch repair and the DNA damage response to ionizing radiation:making sense of apparently conflicting data

The DNA mismatch repair (MMR) pathway detects and repairs DNA replication errors. While DNA MMR-proficiency is known to play a key role in the sensitivity to a number of DNA damaging agents, its role in the cytotoxicity of ionizing radiation (IR) is less well characterized. Available literature to date is conflicting regarding the influence of MMR status on radiosensitivity, and this has arisen as a subject of controversy in the field. The aim of this paper is to provide the first comprehensive overview of the experimental data linking MMR proteins and the DNA damage response to IR. A PubMed search was conducted using the key words "DNA mismatch repair" and "ionizing radiation". Relevant articles and their references were reviewed for their association between DNA MMR and IR. Recent data suggest that radiation dose and the type of DNA damage induced may dictate the involvement of the MMR system in the cellular response to IR. In particular, the literature supports a role for the MMR system in DNA damage recognition, cell cycle arrest, DNA repair and apoptosis. In this review we discuss our current understanding of the impact of MMR status on the cellular response to radiation in mammalian cells gained from past and present studies and attempt to provide an explanation for how MMR may determine the response to radiation.

Induction and antagonism of antiviral responses in respiratory syncytial virus-infected pediatric airway epithelium.

Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well- differentiated pediatric primary bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV disease in infants. RSV is the most important respiratory viral pathogen in young infants worldwide. We found that RSV induces a potent antiviral state in WD-PBECs that was mediated in part by secreted factors, including interferon lambda-1 (IFNλ1)/IL-29. In contrast, type I interferons were not detected following RSV infection of WD-PBECs., Interferon (IFN) responses in RSV-infected WD-PBECs reflected those in lower airway samples from RSV-hospitalized infants. In view of the prominence of IL-29, we determined whether recombinant IL-29 treatment of WD-PBECs before or after infection abrogated RSV replication. Interestingly, IL-29 demonstrated prophylactic, but not therapeutic, potential against RSV. The absence of therapeutic potential reflected effective RSV antagonism of IFN-mediated antiviral responses in infected cells. Our data are consistent with RSV non-structural proteins 1 and/or 2 perturbing the Jak-STAT signaling pathway, with concomitant reduced expression of antiviral effector molecules, such as MxA/B. Antagonism of Jak-STAT signaling was restricted to RSV-infected cells in WD-PBEC cultures. Importantly, our study provides the rationale to further explore IL-29 as a novel RSV prophylactic.

Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

Respiratory Syncytial Virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanised monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F-protein with subnanomolar affinity. ALX-0171 demonstrated superior in vitro neutralisation compared to palivizumab against prototypic RSV A and B strains. Moreover, ALX-0171 completely blocked replication below limit of detection in 87% of the viruses tested versus 18% for palivizumab at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.

Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes

BACKGROUND: Evidence suggests that genetic factors may influence both schizophrenia (Scz) and its clinical presentation. In recent years, genome-wide association studies (GWAS) have demonstrated considerable success in identifying risk loci. Detection of "modifier loci" has the potential to further elucidate underlying disease processes.

METHODS: We performed GWAS of empirically derived positive and negative symptom scales in Irish cases from multiply affected pedigrees and a larger, independent case-control sample, subsequently combining these into a large Irish meta-analysis. In addition to single-SNP associations, we considered gene-based and pathway analyses to better capture convergent genetic effects, and to facilitate biological interpretation of these findings. Replication and testing of aggregate genetic effects was conducted using an independent European-American sample.

RESULTS: Though no single marker met the genome-wide significance threshold, genes and ontologies/pathways were significantly associated with negative and positive symptoms; notably, NKAIN2 and NRG1, respectively. We observed limited overlap in ontologies/pathways associated with different symptom profiles, with immune-related categories over-represented for negative symptoms, and addiction-related categories for positive symptoms. Replication analyses suggested that genes associated with clinical presentation are generalizable to non-Irish samples.

CONCLUSIONS: These findings strongly support the hypothesis that modifier loci contribute to the etiology of distinct Scz symptom profiles. The finding that previously implicated "risk loci" actually influence particular symptom dimensions has the potential to better delineate the roles of these genes in Scz etiology. Furthermore, the over-representation of distinct gene ontologies/pathways across symptom profiles suggests that the clinical heterogeneity of Scz is due in part to complex and diverse genetic factors.

Osteogenic cell response to 3-D hydroxyapatite scaffolds developed via replication of natural marine sponges

Bone tissue engineering may provide an alternative to autograft, however scaffold optimisation is required to maximize bone ingrowth. In designing scaffolds, pore architecture is important and there is evidence that cells prefer a degree of non-uniformity. The aim of this study was to compare scaffolds derived from a natural porous marine sponge (Spongia agaricina) with unique architecture to those derived from a synthetic polyurethane foam. Hydroxyapatite scaffolds of 1 cm3 were prepared via ceramic infiltration of a marine sponge and a polyurethane (PU) foam. Human foetal osteoblasts (hFOB) were seeded at 1x105 cells/scaffold for up to 14 days. Cytotoxicity, cell number, morphology and differentiation were investigated. PU-derived scaffolds had 84-91% porosity and 99.99% pore interconnectivity. In comparison marine sponge-derived scaffolds had 56-61% porosity and 99.9% pore interconnectivity. hFOB studies showed that a greater number of cells were found on marine sponge-derived scaffolds at than on the PU scaffold but there was no significant difference in cell differentiation. X-ray diffraction (XRD) and inductively coupled plasma mass spectrometry (ICP-MS) showed that Si ions were released from the marine-derived scaffold. In summary, three dimensional porous constructs have been manufactured that support cell attachment, proliferation and differentiation but significantly more cells were seen on marine-derived scaffolds. This could be due both to the chemistry and pore architecture of the scaffolds with an additional biological stimulus from presence of Si ions. Further in vivo tests in orthotopic models are required but this marine-derived scaffold shows promise for applications in bone tissue engineering.