Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension

Arterial pulsations are thought to drive CSF flow through perivascular spaces (PVSs), but this has never been quantitatively shown. Using particle tracking to quantify CSF flow velocities in PVSs of live mice, the authors show that flow speeds match the instantaneous speeds of the pulsing artery walls that form the inner boundaries of the PVSs

Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways

Background: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host. Methodology/Principal Findings: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior. Conclusions: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context

Margarita de Sossa, Sixteenth-Century Puebla de los Ángeles, New Spain (Mexico)

Margarita de Sossa’s freedom journey was defiant and entrepreneurial. In her early twenties, still enslaved in Portugal, she took possession of her body; after refusing to endure her owner’s sexual demands, he sold her, and she was transported to Mexico. There, she purchased her freedom with money earned as a healer and then conducted an enviable business as an innkeeper. Sossa’s biography provides striking insights into how she conceptualized freedom in terms that included – but was not limited to – legal manumission. Her transatlantic biography offers a rare insight into the life of a free black woman (and former slave) in late sixteenth-century Puebla, who sought to establish various degrees of freedom for herself. Whether she was refusing to acquiesce to an abusive owner, embracing entrepreneurship, marrying, purchasing her own slave property, or later using the courts to petition for divorce. Sossa continued to advocate on her own behalf. Her biography shows that obtaining legal manumission was not always equivalent to independence and autonomy, particularly if married to an abusive husband, or if financial successes inspired the envy of neighbors

PREVALENCE AND RISK FACTORS OF SCHISTOSOMIASIS AMONG HAUSA COMMUNITIES IN KANO STATE, NIGERIA

SUMMARY Schistosomiasis remains one of the most prevalent neglected tropical diseases especially in Nigeria which has the greatest number of infected people worldwide. A cross-sectional study was conducted among 551 participants from Kano State, North Central Nigeria. Fecal samples were examined for the presence of Schistosoma mansoni eggs using the formalin-ether sedimentation method while the urine samples were examined using the filtration technique for the presence of S. haematobium eggs. Demographic, socioeconomic and environmental information was collected using a pre-validated questionnaire. The overall prevalence of schistosomiasis was 17.8%, with 8.9% and 8.3% infected with S. mansoni and S. haematobium, respectively and 0.5% presenting co-infection with both species. The multiple logistic regression analysis revealed that age < 18 years (OR = 2.13; 95% CI; 1.34- 3.41), presence of infected family members (OR = 3.98; 95% CI; 2.13-7.46), and history of infection (OR = 2.87; 95% CI; 1.87- 4.56) were the significant risk factors associated with schistosomiasis in these communities. In conclusion, this study revealed that schistosomiasis is still prevalent among Hausa communities in Nigeria. Mass drug administration, health education and community mobilization are imperative strategies to significantly reduce the prevalence and morbidity of schistosomiasis in these communities

Health education and the control of intestinal worm infections in China : a new vision

The transmission of soil-transmitted helminths (STHs) is associated with poverty, poor hygiene behaviour, lack of clean water and inadequate waste disposal and sanitation. Periodic administration of benzimidazole drugs is the mainstay for global STH control but it does not prevent re-infection, and is unlikely to interrupt transmission as a stand-alone intervention.; We reported recently on the development and successful testing in Hunan province, PR China, of a health education package to prevent STH infections in Han Chinese primary school students. We have recently commenced a new trial of the package in the ethnically diverse Xishuangbanna autonomous prefecture in Yunnan province and the approach is also being tested in West Africa, with further expansion into the Philippines in 2015.; The work in China illustrates well the direct impact that health education can have in improving knowledge and awareness, and in changing hygiene behaviour. Further, it can provide insight into the public health outcomes of a multi-component integrated control program, where health education prevents re-infection and periodic drug treatment reduces prevalence and morbidity

L-Wnt3a stimulates the survival, proliferation, and engraftment of bone marrow cells.

<p>(A) Aged BMT were treated with L-PBS or (B) L-Wnt3a with an effective concentration = 150 ng/ml, then transplanted into a skeletal defect and after 12 h, analyzed for DNA fragmentation associated with cell apoptosis using TUNEL. (C) Quantification of caspase activity in aged BM treated with L-PBS (grey bar; N = 4) or L-Wnt3a (blue bar; N = 4). (D) Quantification of Ki67 immunostaining for aged BM treated with (E) L-PBS or (F) L-Wnt3a, then transplanted into a skeletal defect and after 12 h analyzed for cell proliferation. (G) FACS analyses of L-PBS treated BMT, harvested from the defect site on post-transplant day 5. (H) FACS analyses of L-Wnt3a treated BMT, harvested from the defect site on post-transplant day 5. (I) GFP immunostaining identifies the L-PBS treated BMT on post-transplant day 7 (J) GFP immunostaining identifies the L-Wnt3a treated BMT on post-transplant day 7. (K) GFP immunostaining shown in higher magnification demonstrating L-PBS treated BMT on post-transplant day 7 (L) GFP immunostaining shown in higher magnification demonstrating L-Wnt3a treated BMT on post-transplant day 7 (M) Histomorphometric quantification of GFP immunopositive cells in the defect site on post-transplant day 7 (N = 5 for each condition). Abbreviations: GFP: green fluorescent protein; TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling; Scale bars: A,B: 50 µm E,F: 100 µm; I,J: 200 µm; K,L: 50 µm.</p

L-Wnt3a activates Wnt/beta-catenin pathway responses in a variety of cell types.

<p>Quantitative RT-PCR analyses demonstrate that in (A) primary mouse embryonic fibroblasts and (B) BM-derived mesenchymal stem cells, <i>Axin2</i> expression shows a dose-dependent increase in response to increasing L-Wnt3a concentrations. (C) MEFs were incubated with L-PBS (grey line) or L-Wnt3a for varying amounts of time. After 2 h, L-Wnt3a induces <i>Axin2</i> expression, just above baseline. After 4 h, L-Wnt3a induced <i>Axin2</i> expression has increased 3-fold (blue line). Following a 2 h-incubation with L-Wnt3a the media is removed and incubation continues for varying amounts of time (dashed blue line). 2 h after wash off, <i>Axin2</i> expression starts steadily declining and returns to baseline at 12 h. (D) MEFs were incubated with vehicle (grey line) or L-Wnt3a (blue line) for up to 24 h. After 3 h, L-Wnt3a represses <i>Sox9</i> expression and keeps it repressed through 24 h of incubation.</p

Wnt3a associates with the liposomal surface.

<p>(A) The rate of Wnt activity partitioning into the liposomal pellet is shown; initially, all Wnt activity (blue lines) is found in the supernatant but within 30 min, the majority of Wnt activity is associated with the liposomal pellet and by 6 h, 90% of Wnt activity is found in the liposomal pellet. (B) Immunoblot analysis using Wnt3a antibody shows that similar to the Wnt activity, initially the majority of the Wnt is found in the supernatant (supnt); within 30 min majority of the majority of Wnt3a segregates into the liposomal pellet and by 6 h 90% of the protein is associated with the liposomal pellet. (C) Following ultra-centrifugation, the majority of the protein is found in the liposomal pellet. (D) Wnt activity (blue bar) is also found in the pellet. Although some Wnt3a is found in the aqueous supernatant, it is inactive (figure C). (E) Sucrose density gradient centrifugation and phospholipid quantification assay (orange line), demonstrate that PBS liposomes migrate to higher density fractions. (F) Sucrose density gradient centrifugation, phosphatidyl choline lipid quantification and Wnt reporter assay, demonstrate that Wnt activity (blue line), the lipids (orange line), co-fractionate on a sucrose density gradient. (G) Immunoblotting analyses using Wnt3a antibody show that Wnt co-migrates with fractions showing maximum Wnt activity and lipid concentration. (H) The stability of L-Wnt3a is measured. At 4°C, L-Wnt3a retains >80% of its activity after extended storage. (I) An anti-Wnt3a immunoblot reveals no evidence of degradation products of L-Wnt3a after extended storage. Data are mean ±SEM from, or are representative of, at least three independent replicates.</p

Wnt3a requires a hydrophobic carrier to maintain its biological activity.

<p>To generate “Wnt3a+CHAPS” (red), 30 ng/µL of Wnt3a protein was diluted in a buffer containing 1× PBS, 0.5 M NaCl, and 1% CHAPS yielding a final CHAPS concentration of 1% and final Wnt3a concentration of 1.95 ng/µL. To generate “Wnt3a−CHAPS” (green), 30 ng/µL Wnt3a protein was diluted in a buffer containing 1× PBS and 0.5 M NaCl yielding a final CHAPS concentration of 0.004% and final Wnt3a concentration of 1.95 ng/µL. Aliquots of each solution were incubated at 23°C for the indicated times, then applied to LSL cells (see Methods). The output of the LSL assay is luciferase activity/beta galactosidase activity (i.e., luc/lac); percent activity is defined as % activity = , where 100% activity = 0.05 ng/µL Wnt3a. (A) After 24 h at room temperature, Wnt3a+CHAPS retains of its 98.0% activity (red line) whereas Wnt3a−CHAPS (green line) retains 11.4% of its activity. (B) Anti-Wnt3a immunoblotting confirms that equivalent amounts of Wnt3a protein were present in both +CHAPS and −CHAPS conditions at the beginning (0 h) and conclusion (24 h) of the incubation period. (C) Immunoblot analysis confirms that in the presence of CHAPS Wnt co-fractionates with lower density sucrose fractions (#1–3). In the absence of CHAPS the protein precipitates as the majority of the protein is found in a high density fraction (lower panel). (D) Sucrose density gradient centrifugation and Wnt reporter assay, demonstrate that in the presence of CHAPS, Wnt activity (red line) migrate to lower density fractions. Without CHAPS, Wnt activity is not detected (green line) (E) To generate “Wnt3a+lipids” (blue), 30 ng/µL of Wnt3a protein was diluted in DMPC∶cholesterol 90∶10 lipid mixture containing 1× PBS yielding a final lipid concentration of 14 µmoles and final Wnt3a concentration of 1.95 ng/µL. To generate “Wnt3a−lipids” (green), 30 ng/µL Wnt3a protein was diluted in a buffer containing 1× PBS and 0.5 M NaCl yielding a final CHAPS concentration of 0.004% and final Wnt3a concentration of 1.95 ng/µL. Both the samples were incubated at room temperature for 24 h. (F) Anti-Wnt3a immunoblotting confirms that equivalent amounts of Wnt3a protein were present in both +lipids and −lipids conditions at the beginning (0 h) and conclusion (24 h) of the incubation period. Data are mean ±SEM from, or are representative of, at least three independent replicates. (G) Wnt3a incubated in the presence of CHAPS (red bar) and lipids (blue bar) for 6 h at room temperature. Wnt3a samples were prepared as described in (A) and (E). (H) Wnt3a incubated in the presence of CHAPS (red bar) and lipids (blue bar) for 6 h at 37°C.</p