Growth factors: a role in guiding axons?

A remarkable finding to emerge in recent years is that the early brain neuroepithelium is highly patterned before axonogenesis begins. Growth factors are among a variety of classes of molecules whose regionalized expression divides the early brain into molecularly distinct domains. Thus, when axons first grow to their synaptic targets, growth factor signalling may help them to navigate. This review discusses recent studies that reveal that growth factors can act as chemoattractants and repellents and that growth factor signalling is important for target entry. These new findings raise the compelling idea that growth factors play an active role in axon navigation.     

Partial purification and characterization of rhinoceros gonadotropins, growth hormone, and prolactin: comparison with the horse and sheep

The rhinoceros is an endangered species related to the horse family. Little is known of its reproductive endocrinology. The objectives of this study were to partially purify rhinoceros pituitary hormones, determine which assays could be used for their assessment, and to ascertain whether rhinoceros LH possesses the intrinsic FSH activity of equine LH. A single pituitary each from a White (1.3 g) and a Black (1.2 g) Rhinoceros was homogenized and extracted (pH 9.5), then subjected to pH and salt fractionation, and ion-exchange chromatography (DEAE and Sephadex SP-C50) to yield partially purified fractions of LH, FSH, growth hormone (GH), and prolactin (PRL). LH was readily measured by a rat Leydig cell assay (0.1-1% x equine LH) and an RIA using a monoclonal antibody to bovine LH (6-11% x equine LH). FSH activity detected in the LH by either an FSH RIA or a calf testis radioreceptor assay (RRA) was extremely low. No FSH activity could be detected in the White Rhinoceros pituitary "FSH" fraction, but was readily detected in the Black Rhinoceros fraction (RIA: 0.2% x equine FSH: RRA: 0.8% x equine FSH). The presence of GH and PRL was determined by SDS-PAGE and Western blots. Results showed a single immunoreactive GH band and multiple immunoreactive PRL bands. Adsorption with Concanavalin A-Sepharose indicated that some of the PRL bands are glycosylated.     

Biological and immunoactive substances resembling chorionic gonadotropin are present in full-term horse and zebra placentas.

This study describes the presence of immunoactive and bioactive eCG-like material in full-term placentas of both domestic horses and zebras. Term placental extracts were immunoreactive in an LH monoclonal antibody RIA, and methods successfully used previously for the purification of eCG and eLH were employed to further concentrate the immunoreactive materials to the point where additional characterization studies could be performed. Sufficient equine material was obtained to perform a final fractionation on a concanavalin A Sepharose column yielding an unadsorbed fraction, e17A, and an adsorbed fraction, e17B. There was insufficient zebra material, z5D, for this step. HPLC gel filtration coupled with LH immunoassays of the column eluates showed all the final placental fractions to be highly heterogeneous, but a discrete peak of immunoactivity was found in one of the two equine fractions (e17B) and in the zebra fraction (z5D). The HPLC gel filtration elution volumes for e17B and z5D suggest that they have a smaller molecular size than either eCG or eLH but almost the same size as ovine LH. Both e17B and z5D were bioactive in the rat Leydig cell assay for LH but low in potency compared to eCG or eLH; e17A was inactive at very high doses (5 micrograms). This latter fraction, however, cross-reacted in an eCG alpha RIA to a much greater extent (6 times) than e17B, suggesting that it may be an incompletely formed or degraded alpha subunit. RIAs for LH, eCG, and eCG beta suggest that epitopes distinctive for these molecules are also present or similar to those in the term placental materials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Zebra chorionic gonadotropin: partial purification and characterization

Six samples of pregnant zebra (z) serum from the first and second trimesters of pregnancy were analyzed by RIA and shown to have chorionic gonadotropin levels comparable to that of the mare (0.9-5.3 micrograms/ml); first trimester levels in most cases were higher than second trimester levels. A pool of the sera (10 ml) was fractionated by methods previously employed for the purification of equine (e) and donkey (d) chorionic gonadotropin to achieve a concentration of the zebra chorionic gonadotropin (zCG). A yield of 1.0 mg of glycoprotein was obtained. HPLC analysis of the material indicated the content of zCG to be about 7%. Its molecular size as judged by Ve/Vo values is smaller than eCG, greater than ovine LH, and about the same as equine LH. The zCG was tested in RIAs for LH and eCG, radioreceptor assays (RRA) for LH and FSH, and the rat testis Leydig cell assay for LH. Comparisons were made with equine and donkey chorionic gonadotropin, and equine and zebra LH. The results, preliminary because the preparation is not of high purity, showed that zCG is bioactive as an LH; immunologically similar to eCG, eLH, dCG, and zLH; and competes in RRAs for LH but not FSH receptors. It differs, therefore, from eCG and eLH--which have high levels of intrinsic FSH activity, and is more like dCG, dLH, and zLH--all of which have minimal if any FSH activity.     

Immune Complexes in Cystic Fibrosis

Circulating immune complexes were detected in serum and sputum of patients with cystic fibrosis (C.F.). There were extensive deposits of immunoglobulins and complement immune complexes in several of the C.F. organs, especially the respiratory and gastrointestinal tracts, but not in the kidneys. Significant concentrations of IgG and of complement complexes could be eluted from the lungs of the C.F. patients but not from those of controls. Studies involving immunoabsorption, autoradiography, and molecular sieving through Sephadex G-200 columns identified both bovine serum albumin and staphylococcal α-haemolysin as two of the antigens present in the immune complexes. The sedimentation constant of the immune complexes was about 8S to 11S. The clinical significance of these immune complexes and the wide variety of antibodies detected in C.F. patients are discussed.     

Active Video Games and Health Indicators in Children and Youth: A Systematic Review

Background

Active video games (AVGs) have gained interest as a way to increase physical activity in children and youth. The effect of AVGs on acute energy expenditure (EE) has previously been reported; however, the influence of AVGs on other health-related lifestyle indicators remains unclear.

Objective

This systematic review aimed to explain the relationship between AVGs and nine health and behavioural indicators in the pediatric population (aged 0–17 years).

Data sources

Online databases (MEDLINE, EMBASE, psycINFO, SPORTDiscus and Cochrane Central Database) and personal libraries were searched and content experts were consulted for additional material.

Data selection

Included articles were required to have a measure of AVG and at least one relevant health or behaviour indicator: EE (both habitual and acute), adherence and appeal (i.e., participation and enjoyment), opportunity cost (both time and financial considerations, and adverse events), adiposity, cardiometabolic health, energy intake, adaptation (effects of continued play), learning and rehabilitation, and video game evolution (i.e., sustainability of AVG technology).

Results

51 unique studies, represented in 52 articles were included in the review. Data were available from 1992 participants, aged 3–17 years, from 8 countries, and published from 2006–2012. Overall, AVGs are associated with acute increases in EE, but effects on habitual physical activity are not clear. Further, AVGs show promise when used for learning and rehabilitation within special populations. Evidence related to other indicators was limited and inconclusive.

Conclusions

Controlled studies show that AVGs acutely increase light- to moderate-intensity physical activity; however, the findings about if or how AVG lead to increases in habitual physical activity or decreases in sedentary behaviour are less clear. Although AVGs may elicit some health benefits in special populations, there is not sufficient evidence to recommend AVGs as a means of increasing daily physical activity.     

Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey

Background:

Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults.

Methods:

We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status.

Results:

The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m² or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%).

Interpretation:

The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease.Chronic kidney disease is defined as the presence of kidney damage or reduced kidney function for more than 3 months and requires either a measured or estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m², or the presence of abnormalities in urine sediment, renal imaging or biopsy results.¹ Between 1.3 million and 2.9 million Canadians are estimated to have chronic kidney disease, based on an extrapolation of the prevalence of end-stage renal disease.² In the United States, the 1999–2004 National Health and Nutrition Examination Survey reported a prevalence of 5.0% for stage 1 and 2 disease and 8.1% for stage 3 and 4 disease.^3,4Chronic kidney disease has been identified as a risk factor for death and cardiovascular-related morbidity and is a substantial burden on the health care system.^1,5 Hemodialysis costs the Canadian health care system about $60 000 per patient per year of treatment.¹ The increasing prevalence of chronic kidney disease can be attributed in part to the growing elderly population and to increasing rates of diabetes and hypertension.^1,6,7Albuminuria, which can result from abnormal vascular permeability, atherosclerosis or renal disease, has gained recognition as an independent risk factor for progressive renal dysfunction and adverse cardiovascular outcomes.^8–10 In earlier stages of chronic kidney disease, albuminuria has been shown to be more predictive of renal and cardiovascular events than eGFR.^4,9 This has prompted the call for a new risk stratification for cardiovascular outcomes based on both eGFR and albuminuria.¹¹A recent review advocated screening people for chronic kidney disease if they have hypertension, diabetes, clinically evident cardiovascular disease or a family history of kidney failure or are more than 60 years old.⁴ The Canadian Society of Nephrology published guidelines on the management of chronic kidney disease but did not offer guidance on screening.¹ The Canadian Diabetes Association recommends annual screening with the use of an albumin:creatinine ratio,¹² and the Canadian Hypertension Education Program guideline recommends urinalysis as part of the initial assessment of hypertension.¹³ Screening for chronic kidney disease on the basis of eGFR and albuminuria is not considered to be cost-effective in the general population, among older people or among people with hypertension.¹⁴The objective of our study was to use direct measures (biomarkers) of kidney function to generate nationally representative, population-based prevalence estimates of chronic kidney disease among Canadian adults overall and in clinically relevant groups.     

Patterning and Lifetime of Plasma Membrane-Localized Cellulose Synthase Is Dependent on Actin Organization in Arabidopsis Interphase Cells

The actin and microtubule cytoskeletons regulate cell shape across phyla, from bacteria to metazoans. In organisms with cell walls, the wall acts as a primary constraint of shape, and generation of specific cell shape depends on cytoskeletal organization for wall deposition and/or cell expansion. In higher plants, cortical microtubules help to organize cell wall construction by positioning the delivery of cellulose synthase (CesA) complexes and guiding their trajectories to orient newly synthesized cellulose microfibrils. The actin cytoskeleton is required for normal distribution of CesAs to the plasma membrane, but more specific roles for actin in cell wall assembly and organization remain largely elusive. We show that the actin cytoskeleton functions to regulate the CesA delivery rate to, and lifetime of CesAs at, the plasma membrane, which affects cellulose production. Furthermore, quantitative image analyses revealed that actin organization affects CesA tracking behavior at the plasma membrane and that small CesA compartments were associated with the actin cytoskeleton. By contrast, localized insertion of CesAs adjacent to cortical microtubules was not affected by the actin organization. Hence, both actin and microtubule cytoskeletons play important roles in regulating CesA trafficking, cellulose deposition, and organization of cell wall biogenesis.Plant cells are surrounded by a flexible yet durable extracellular matrix that makes up the cell wall. This structure offers mechanical strength that counters osmotically driven turgor pressure, is an important factor for water movement in plants, acts as a physical barrier against pathogens (Somerville et al., 2004), and is a determining factor for plant cell morphogenesis. Hence, the cell wall plays a central role in plant biology.Two main types of cell walls can typically be distinguished: the primary and the secondary cell wall. The major load-bearing component in both of these cell walls is the β-1,4-linked glucan polymer cellulose (Somerville et al., 2004). Cellulose polymers are synthesized by plasma membrane (PM)-localized cellulose synthase (CesA) complexes (Mueller and Brown, 1980), which contain several CesA subunits with similar amino acid sequences (Mutwil et al., 2008a). The primary wall CesA complexes are believed to be assembled in the Golgi and are subsequently delivered to the PM via vesicular trafficking (Gutierrez et al., 2009), sometimes associated with Golgi pausing (Crowell et al., 2009). Furthermore, the primary wall CesA complexes are preferentially inserted into the PM at sites that coincide with cortical microtubules (MTs), which subsequently guide cellulose microfibril deposition (Gutierrez et al., 2009). Hence, the cortical MT array is a determinant for multiple aspects of primary wall cellulose production.The actin cytoskeleton plays a crucial role in organized deposition of cell wall polymers in many cell types, including cellulose-related polymers and pectins in tip-growing cells, such as pollen tubes and root hairs (Hu et al., 2003; Chen et al., 2007). Thus, actin-depolymerizing drugs and genetic manipulation of ACTIN genes impair directed expansion of tip-growing cells and long-distance transport of Golgi bodies with vesicles to growing regions (Ketelaar et al., 2003; Szymanski, 2005). In diffusely growing cells in roots and hypocotyls, loss of anisotropic growth has also been observed in response to mutations to vegetative ACTIN genes and to actin-depolymerizing and -stabilizing drugs (Baluska et al., 2001; Kandasamy et al., 2009). While actin is clearly important for cell wall assembly, it is less clear what precise roles it plays.One well-known function of actin in higher plants is to support intracellular movement of cytoplasmic organelles via actomyosin-based motility (Geisler et al., 2008; Szymanski, 2009). During primary wall synthesis in interphase cells, treatment with the actin assembly inhibitor latrunculin B (LatB) led to inhibition of Golgi motility and pronounced inhomogenities in CesA density at the PM (Crowell et al., 2009; Gutierrez et al., 2009) that coincided with the density of underlying and immobile Golgi bodies (Gutierrez et al., 2009). These results suggested that Golgi motility is important for CesA distribution (Gutierrez et al., 2009). The actin cytoskeleton also appears to be important for secondary wall cellulose microfibril deposition. For example, longitudinal actin filaments (AFs) define the movement of secondary wall CesA-containing Golgi bodies in developing xylem vessels (Wightman and Turner, 2008). In addition, it has been proposed that the AFs also can regulate the delivery of the secondary wall CesA complex to the PM via pausing of the Golgi (Wightman and Turner, 2008). It is therefore clear that actin organization is important for CesA distribution and for the pattern of cellulose microfibril deposition.Despite the above findings, very few reports have undertaken detailed studies to elucidate the role of the actin cytoskeleton in the distribution and trafficking of specific proteins in plant cells. Here, we have investigated the intracellular trafficking of CesA-containing vesicles and delivery of CesAs to the PM, in the context of the actin cytoskeleton. We quantitatively demonstrate that the organization of the actin cytoskeleton regulates CesA-containing Golgi distribution and the exocytic and endocytic rate of the CesAs. However, actin organization has no effect on the localized insertion of CesAs at sites of MTs at the PM.     

Excess Cardiovascular Risk Burden in Jamaican Women Does Not Influence Predicted 10-Year CVD Risk Profiles of Jamaica Adults: An Analysis of the 2007/08 Jamaica Health and Lifestyle Survey

Background

Black Caribbean women have a higher burden of cardiovascular disease (CVD) risk factors than their male counterparts. Whether this results in a difference in incident cardiovascular events is unknown. The aim of this study was to estimate the 10 year World Health Organization/International Society for Hypertension (WHO/ISH) CVD risk score for Jamaica and explore the effect of sex as well as obesity, physical activity and socioeconomic status on these estimates.

Methods and Findings

Data from 40–74 year old participants in the 2007/08 Jamaica Health and Lifestyle Survey were used. Trained interviewers administered questionnaires and measured anthropometrics, blood pressure, fasting glucose and cholesterol. Education and occupation were used to assess socioeconomic status. The Americas B tables were used to estimate the WHO/ISH 10 year CVD risk scores for the population. Weighted prevalence estimates were calculated. Data from 1,432 (450 men, 982 women) participants were analysed, after excluding those with self-reported heart attack and stroke. The women had a higher prevalence of diabetes (19%W;12%M), hypertension (49%W;47%M), hypercholesterolemia (25%W;11%M), obesity (46%W;15%M) and physical inactivity (59%W;29%M). More men smoked (6%W;31%M). There was good agreement between the 10-year cardiovascular risk estimates whether or not cholesterol measurements were utilized for calculation (kappa –0.61). While 90% had a 10 year WHO/ISH CVD risk of less than 10%, approximately 2% of the population or 14,000 persons had a 10 year WHO/ISH CVD risk of ≥30%. As expected CVD risk increased with age but there was no sex difference in CVD risk distribution despite women having a greater risk factor burden. Women with low socioeconomic status had the most adverse CVD risk profile.

Conclusion

Despite women having a higher prevalence of CVD risk factors there was no sex difference in 10-year WHO/ISH CVD risk in Jamaican adults.