Chitosan Glutamate-Coated Niosomes: a proposal for Nose-to-Brain delivery

The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM). Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration

Widespread Presence of Human BOULE Homologs among Animals and Conservation of Their Ancient Reproductive Function

Sex-specific traits that lead to the production of dimorphic gametes, sperm in males and eggs in females, are fundamental for sexual reproduction and accordingly widespread among animals. Yet the sex-biased genes that underlie these sex-specific traits are under strong selective pressure, and as a result of adaptive evolution they often become divergent. Indeed out of hundreds of male or female fertility genes identified in diverse organisms, only a very small number of them are implicated specifically in reproduction in more than one lineage. Few genes have exhibited a sex-biased, reproductive-specific requirement beyond a given phylum, raising the question of whether any sex-specific gametogenesis factors could be conserved and whether gametogenesis might have evolved multiple times. Here we describe a metazoan origin of a conserved human reproductive protein, BOULE, and its prevalence from primitive basal metazoans to chordates. We found that BOULE homologs are present in the genomes of representative species of each of the major lineages of metazoans and exhibit reproductive-specific expression in all species examined, with a preponderance of male-biased expression. Examination of Boule evolution within insect and mammalian lineages revealed little evidence for accelerated evolution, unlike most reproductive genes. Instead, purifying selection was the major force behind Boule evolution. Furthermore, loss of function of mammalian Boule resulted in male-specific infertility and a global arrest of sperm development remarkably similar to the phenotype in an insect boule mutation. This work demonstrates the conservation of a reproductive protein throughout eumetazoa, its predominant testis-biased expression in diverse bilaterian species, and conservation of a male gametogenic requirement in mice. This shows an ancient gametogenesis requirement for Boule among Bilateria and supports a model of a common origin of spermatogenesis

VISTA Variables in the <i>Vía Láctea</i> (VVV): Halfway Status and Results

The VISTA Variables in the Vía Láctea (VVV) survey is one of six near-infrared ESO public surveys, and is now in its fourth year of observing. Although far from being complete, the VVV survey has already delivered many results, some directly connected to the intended science goals (detection of variable stars, microlensing events, new star clusters), others concerning more exotic objects, e.g., novae. Now, at the end of the fourth observing period, and comprising roughly 50% of the proposed observations, the status of the survey, as well some of results based on the VVV data, are presented.Facultad de Ciencias Astronómicas y Geofísica

Sonic hedgehog protein is decreased and penile morphology is altered in prostatectomy and diabetic patients.

Erectile dysfunction (ED) is a debilitating medical condition and current treatments are ineffective in patients with cavernous nerve (CN) injury, due to penile remodeling and apoptosis. A critical regulator of penile smooth muscle and apoptosis is the secreted protein sonic hedgehog (SHH). SHH protein is decreased in rat prostatectomy and diabetic ED models, SHH inhibition in the penis induces apoptosis and ED, and SHH treatment at the time of CN injury suppresses smooth muscle apoptosis and promotes regeneration of erectile function. Thus SHH treatment has significant translational potential as an ED therapy if similar mechanisms underlie ED development in patients. In this study we quantify SHH protein and morphological changes in corpora cavernosal tissue of control, prostatectomy and diabetic patients and hypothesize that decreased SHH protein is an underlying cause of ED development in prostatectomy and diabetic patients. Our results show significantly decreased SHH protein in prostatectomy and diabetic penis. Morphological remodelling of the penis, including significantly increased apoptotic index and decreased smooth muscle/collagen ratio, accompanies declining SHH. SHH signaling is active in human penis and is altered in a parallel manner to previous observations in the rat. These results suggest that SHH has significant potential to be developed as an ED therapy in prostatectomy and diabetic patients. The increased apoptotic index long after initial injury is suggestive of ongoing remodeling that may be clinically manipulatable

Elevated Atmospheric CO 2 Alters Soil Microbial Communities Associated with Trembling Aspen ( Populus tremuloides ) Roots

Global atmospheric CO 2 levels are expected to double within the next 50 years. To assess the effects of increased atmospheric CO 2 on soil ecosystems, cloned trembling aspen ( Populus tremuloides ) seedlings were grown individually in 1 m 3 open bottom root boxes under either elevated (720 ppm, ELEV) or ambient CO 2 (360 ppm, AMB). After 5 years, soil cores (40 cm depth) were collected from the root boxes and divided into 0–20 cm and 20–40 cm fractions. ELEV treatment resulted in significant decreases in both soil nitrate and total soil nitrogen in both the 0–20 cm and 20–40 cm soil fractions, with a 47% decrease in soil nitrate and a 50% decrease in total soil nitrogen occurring in the 0–20 cm fraction. ELEV treatment did not result in a significant change in the amount of soil microbial biomass. However, analysis of indicator phospholipid fatty acids (PLFA) indicated that ELEV treatment did result in significant increases in PLFA indicators for fungi and Gram-negative bacteria in the 0–20 cm fraction. Terminal restriction fragment length polymorphism (T-RFLP) analysis was used to analyze the composition of the soil bacterial communities (using primers targeting the 16SrRNA gene) and the soil fungal communities (using primers targeting the intergenic transcribed spacer region). T-RFLP analysis revealed shifts in both bacterial and fungal community structure, as well as increases in both bacterial and fungal species richness with ELEV treatment. These results indicated that increased atmospheric CO 2 had significant effects on both soil nutrient availability and the community composition of soil microbes associated with aspen roots.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48116/1/248_2004_Article_120.pd

Trichrome and TUNEL were performed on corpora cavernosal tissue from control, prostatectomy, and diabetic patients.

<p>The smooth muscle/collagen ratio decreased 25% in prostatectomy and 28% in diabetic penis (p = 0.0338). The apoptotic index increased 22% in prostatectomy and 25% in diabetic penis (p = 0.0141). Arrows indicate staining. 100–400× magnification.</p

Quantification of precursor and active SHH protein by western analysis of corpora cavernosal tissue from control, prostatectomy and diabetic patients.

<p>Precursor SHH protein significantly decreased 41% in prostatectomy and 39% in diabetic patients (p = 0.0312). Active SHH protein significantly decreased 46% in prostatectomy and 48% in diabetic patients in comparison to controls (p = 0.0222). Asterisks indicate significance. Where error bars do not appear they are too small to be shown on the graph.</p

ED severity as measured by IIEF in control, prostatectomy and diabetic patients.

<p>ED severity as measured by IIEF in control, prostatectomy and diabetic patients.</p