A global call for action to include gender in research impact assessment.

Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably).

Participation in paediatric cancer studies: timing and approach to recruitment.

Background: Participation in epidemiological studies has fallen significantly over the past 30 years; this has been attributed to a busier lifestyle and longer working hours. In case-control studies, participation among cases is usually higher than among controls due to the personal relevance. In Australia, between 2003 and 2011, we conducted three national population-based case-control studies of risk factors for childhood cancers; brain tumors, acute leukemia and neuroblastoma and Wilms' tumor.

Participation in population-based case-control studies: does the observed decline vary by socio-economic status?

An Australian study of childhood leukaemia (Aus-ALL) previously reported that control participation was positively associated with socio-economic status (SES). A similar study of childhood brain tumours (Aus-CBT) was carried out 4 years later, and this paper compares control participation and its relationship with SES in the two studies. To assess the representativeness of controls in terms of SES, the addresses of controls were linked to Australian Bureau of Statistics Census 2006 Collection Districts (CDs), and hence to area-based indices of SES.

Tanzanian malignant lymphomas: WHO classification, presentation, ploidy, proliferation and HIV/EBV association.

Background: In Tanzania, the International Working Formulation [WF] rather than the WHO Classification is still being used in diagnosing malignant lymphomas (ML) and the biological characterization including the HIV/EBV association is sketchy, thus restraining comparison, prognostication and application of established therapeutic protocols.

Methods: Archival, diagnostic ML biopsies (N = 336), available sera (N = 35) screened by ELISA for HIV antibodies and corresponding clinical/histological reports at Muhimbili National Hospital (MNH) in Tanzania between 1996 and 2006 were retrieved and evaluated. A fraction (N = 174) were analyzed by histopathology and immunohistochemistry (IHC).

Knee extension and flexion weakness in people with knee osteoarthritis: is antagonist cocontraction a factor?

Study Design: Controlled laboratory study, cross-sectional data.

Objectives: To investigate isometric knee flexion and extension strength, failure of voluntary muscle activation, and antagonist cocontraction of subjects with knee osteoarthritis (OA) compared with age-matched asymptomatic control subjects.

Background: Quadriceps weakness is a common impairment in individuals with knee OA.

Knee joint kinematics, kinetics and muscle co-contraction in knee osteoarthritis patient gait.

Background: Compared to matched controls, knee osteoarthritis patients walk with altered, kinematics, kinetics and muscle activity. Studies of osteoarthritis patient gait have focused on individual measures, and findings from these studies differ due to differences in patient levels of disability and age. Therefore, aims of this study were to examine kinematic, kinetic and muscle co-contraction gait variables within a single osteoarthritis patient group, and to determine if alterations in these variables are related to pain, symptom and function measures.

Interphase FISH on TEL/AML1 positive acute lymphoblastic leukemia relapses--analysis of clinical relevance of additional TEL and AML1 copy number changes.

Objectives: TEL/AML1 (ETV6/RUNX1) fusion resulting from the translocation t(12;21)(p13;q22) constitutes the most common chimeric fusion gene in initial childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) (19-27%) and has been associated with good prognosis. Three secondary aberrations in TEL/AML1 positive ALL have been suspected to negatively influence outcome: deletion of the second TEL allele (T), gain of the second AML1 allele (A) and duplication of the derivative chromosome 21 (der(21), TA). Many studies have explored such aberrations in initial disease, while only few reports have investigated them in relapses.

Potential roles of Arnt2 in zebrafish larval development.

The aryl hydrocarbon receptor nuclear translocator (ARNT) is a basic helix-loop-helix-PAS heterodimeric transcription factor that dimerizes with other basic helix-loop-helix-PAS proteins to mediate biological responses. The function of ARNT2 is poorly understood. Here we provide an initial characterization of the zebrafish arnt2 null (arnt2(-/-)) mutant to identify functions of Arnt2 during development.

Environmental toxicants and effects on female reproductive function.

One of the most toxic substances known to humans, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), is also highly pervasive in the environment. It is created naturally in volcanic eruptions and forest fires, and anthropogenically in waste incineration, chlorination processes and certain plastics manufacture. From reports of large industrial and other accidents, or from experimental studies, dioxin exposure has been correlated in animal models and/or humans with chloracne of the skin, organ cancers, hepatotoxicity, gonadal and immune changes, pulmonary and other diseases such as diabetes, skewing of the sex ratio, and infertility.

Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: insights into TCDD-induced endocrine disruption and reproductive toxicity.

TCDD is a reproductive toxicant and endocrine disruptor, yet the mechanisms by which it causes these reproductive alterations are not fully understood. In order to provide additional insight into the molecular mechanisms that underlie TCDD's reproductive toxicity, we assessed TCDD-induced transcriptional changes in the ovary as they relate to previously described impacts on serum estradiol concentrations and altered follicular development in zebrafish. In silico computational approaches were used to correlate candidate regulatory motifs with observed changes in gene expression.

Developmental toxicity of low generation PAMAM dendrimers in zebrafish.

Biological molecules and intracellular structures operate at the nanoscale; therefore, development of nanomedicines shows great promise for the treatment of disease by using targeted drug delivery and gene therapies. PAMAM dendrimers, which are highly branched polymers with low polydispersity and high functionality, provide an ideal architecture for construction of effective drug carriers, gene transfer devices and imaging of biological systems. For example, dendrimers bioconjugated with selective ligands such as Arg-Gly-Asp (RGD) would theoretically target cells that contain integrin receptors and show potential for use as drug delivery devices.

Identification of the human/mouse syntenic common fragile site FRA7K/Fra12C1--relation of FRA7K and other human common fragile sites on chromosome 7 to evolutionary breakpoints.

Common fragile sites (CFSs) are expressed as chromosome gaps in cells of different species including human and mouse as a result of the inhibition of DNA replication. They may serve as hot spots for DNA breakage in processes such as tumorigenesis and chromosome evolution. Using multicolor fluorescence in situ hybridization mapping, the authors describe here human CFS FRA7K on chromosome band 7q31.

CGH of microdissected Kaposi's sarcoma lesions reveals recurrent loss of chromosome Y in early and additional chromosomal changes in late tumour stages.

Background: It is still unclear if Kaposi's sarcoma (KS) is a monoclonal cell proliferation or a polyclonal, hyperplastic, reactive process. Reports on KS cytogenetics are few and restricted to late stage disease and cell lines.

Method: We analysed 27 KS, early and late, AIDS related (AKS) and endemic (EKS) by laser microdissection, global DNA amplification and comparative genomic hybridization (CGH).

Common fragile sites are conserved features of human and mouse chromosomes and relate to large active genes.

Common fragile sites (CFSs) are seen as chromosomal gaps and breaks brought about by inhibition of replication, and it is thought that they cluster with tumor breakpoints. This study presents a comprehensive analysis using conventional and molecular cytogenetic mapping of CFSs and their expression frequencies in two mouse strains, BALB/c and C57BL/6, and in human probands. Here we show that induced mouse CFSs relate to sites of spontaneous gaps and breaks and that CFS expression levels in chromosome bands are conserved between the two mouse strains and between syntenic mouse and human DNA segments.

Lymphatic and vascular origin of Kaposi's sarcoma spindle cells during tumor development.

The histogenesis of Kaposi's sarcoma (KS) tumor spindle cells (SC) remains controversial but several immunohistochemical studies favor a lymphatic origin. Twenty KS surgical biopsies were analyzed for the coexpression of LANA, CD34, LYVE-1, D2-40, VEGFR-2, VEGFR3 by using double or triple immunostaining. Most of the SC in both early and late KS expressed the lymphatic markers LYVE-1, D2-40 and VEGFR-3 and the blood vascular endothelial/endothelial precursor cell markers CD34 and endothelial stem cell marker VEGFR-2.

Inhibition of follicular development, vitellogenesis, and serum 17beta-estradiol concentrations in zebrafish following chronic, sublethal dietary exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent endocrine disruptor with the ability to affect several biologic processes, including reproduction. In fish, sublethal exposure to TCDD is known to modulate overall reproductive capacity, but impacts on follicular development and vitellogenesis are unknown. Here we show that chronic, dietary exposure to 0.

Adaptations to normal human gait on potentially slippery surfaces: the effects of awareness and prior slip experience.

Prior knowledge of potentially slippery conditions has been shown to alter normal human gait in slip and fall experiments. Here we quantify the effects of two aspects of prior knowledge - awareness of a possible slip and prior slip experience - on normal gait. Sixty-eight subjects (40F, 28M) each walked over 48 high-friction surfaces (control trials) and 12 low-friction surfaces.

The effect of subject awareness and prior slip experience on tribometer-based predictions of slip probability.

Prior knowledge of potentially slippery conditions has been shown to alter normal human gait in slip and fall experiments. We sought to quantify how the empirical relationship between slip probability and available floor friction was affected by subject awareness and prior slip experience. Sixty-eight subjects (40 females, 28 males) walked over three different low-friction surfaces inserted periodically between non-slip control trials.

Dose and time dependent apoptotic response in a human melanoma cell line exposed to accelerated boron ions at four different LET.

The aim was to investigate and compare the influence of linear energy transfer (LET), dose and time on the induction of apoptosis in a human melanoma cell line exposed to accelerated light boron ((10)B) ions and photons. Cells were exposed in vitro to doses up to 6 Gy accelerated boron ions (40, 80, 125 and 160 eV nm(-1)) and up to 12 Gy photons (0.2 eV nm(-1)).

Structure and permeability of the egg capsule of the bonnethead shark, Sphyrna tiburo.

In the viviparous bonnethead shark, Sphyrna tiburo, a fluid-filled, acellular egg capsule surrounds fertilized eggs and developing embryos throughout gestation. Like other placental shark species, the capsule remains intact even at the placental implantation site. Although its intervention between the uterine and embryonic tissues of the placenta has long been thought to mediate physiological exchange, little information is available concerning even its basic structure or permeability to solutes.

Accumulation, tissue distribution, and maternal transfer of dietary 2,3,7,8,-tetrachlorodibenzo-p-dioxin: impacts on reproductive success of zebrafish.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a reproductive toxicant and endocrine disruptor in nearly all vertebrates; however, the mechanisms by which TCDD alters the reproductive system is not well understood. The zebrafish provides a powerful vertebrate model system to investigate molecular mechanisms by which TCDD affects the reproductive system, but little is known regarding reproductive toxic response of zebrafish following chronic, sublethal exposure to TCDD. Here we investigate the accumulation of TCDD in selected tissues of adult female zebrafish and maternal transfer to offspring following dietary exposure to TCDD (0.

Different G2/M accumulation in M059J and M059K cells after exposure to DNA double-strand break-inducing agents.

Purpose: To investigate and compare the cell cycle progression in relation to cell death in the human glioma cell lines, M059J and M059K, after exposure to DNA double-strand break-inducing agents.

Methods And Materials: The M059J and M059K cells, deficient and proficient in the catalytic subunit of the DNA-dependent protein kinase, respectively, were exposed to 1 and 4 Gy of photons or accelerated nitrogen ions. In addition, M059J and M059K cells were treated with 10 and 40 mug/mL of bleomycin for 30 min, respectively.

Epstein-Barr virus LMP1 status in relation to apoptosis, p53 expression and leucocyte infiltration in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) infection. EBV-encoded LMP1, expressed in most of NPC, has been suggested to have an important role in the pathogenesis and development of NPC and its expression correlates with poor prognosis.

Materials And Methods: Eighty-seven NPC biopsies were analyzed by immunohistochemistry for expression of markers of cell proliferation, apoptosis, infiltrating T lymphocytes and macrophages in relation to the LMP1 status.

Human herpesvirus 8/Kaposi sarcoma herpesvirus cell association during evolution of Kaposi sarcoma.

Kaposi sarcoma (KS) is associated with a herpesvirus (HHV-8/KSHV), which expresses a latency-associated nuclear antigen (LANA). The histopathology of KS is characterized by angiogenesis, inflammatory cells, and the development of CD34+ tumor spindle cells (SCs). However, the cellular basis for the recruitment and dissemination of HHV-8 during the development of KS lesions is not clear.

Dichotomy between CD1a+ and CD83+ dendritic cells in lymph nodes during SIV infection of macaques.

The prevalence and differentiation of dendritic cells (DC) in lymphoid tissue of simian immunodeficiency virus (SIV)-infected cynomolgus monkeys was studied during disease progression. Lymph node biopsies were consecutively obtained from clinical rapid and slow progressors until the development of disease consistent with simian acquired immunodeficiency syndrome (sAIDS) occurred. Quantitative evaluation of CD1a+ DC and the expression of DC antigens related to maturation (CD83, DC-LAMP and S100b) were performed at the single cell level by in situ image analysis.