Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium

A decline in stem cell function impairs tissue regeneration during ageing, but the role of the stem-cell-supporting niche in ageing is not well understood. The small intestine is maintained by actively cycling intestinal stem cells that are regulated by the Paneth cell niche(1,2). Here we show that the regenerative potential of human and mouse intestinal epithelium diminishes with age owing to defects in both stem cells and their niche. The functional decline was caused by a decrease in stemness-maintaining Wnt signalling due to production of Notum, an extracellular Wnt inhibitor, in aged Paneth cells. Mechanistically, high activity of mammalian target of rapamycin complex 1 (mTORC1) in aged Paneth cells inhibits activity of peroxisome proliferator activated receptor alpha (PPAR-alpha)(3), and lowered PPAR-a activity increased Notum expression. Genetic targeting of Notum or Wnt supplementation restored function of aged intestinal organoids. Moreover, pharmacological inhibition of Notum in mice enhanced the regenerative capacity of aged stem cells and promoted recovery from chemotherapy-induced damage. Our results reveal a role of the stem cell niche in ageing and demonstrate that targeting of Notum can promote regeneration of aged tissues.Peer reviewe

Ecosystem Services in Conservation Planning: Targeted Benefits vs. Co-Benefits or Costs?

There is growing support for characterizing ecosystem services in order to link conservation and human well-being. However, few studies have explicitly included ecosystem services within systematic conservation planning, and those that have follow two fundamentally different approaches: ecosystem services as intrinsically-important targeted benefits vs. substitutable co-benefits. We present a first comparison of these two approaches in a case study in the Central Interior of British Columbia. We calculated and mapped economic values for carbon storage, timber production, and recreational angling using a geographical information system (GIS). These ‘marginal’ values represent the difference in service-provision between conservation and managed forestry as land uses. We compared two approaches to including ecosystem services in the site-selection software Marxan: as Targeted Benefits, and as Co-Benefits/Costs (in Marxan's cost function); we also compared these approaches with a Hybrid approach (carbon and angling as targeted benefits, timber as an opportunity cost). For this analysis, the Co-Benefit/Cost approach yielded a less costly reserve network than the Hybrid approach (1.6% cheaper). Including timber harvest as an opportunity cost in the cost function resulted in a reserve network that achieved targets equivalently, but at 15% lower total cost. We found counter-intuitive results for conservation: conservation-compatible services (carbon, angling) were positively correlated with each other and biodiversity, whereas the conservation-incompatible service (timber) was negatively correlated with all other networks. Our findings suggest that including ecosystem services within a conservation plan may be most cost-effective when they are represented as substitutable co-benefits/costs, rather than as targeted benefits. By explicitly valuing the costs and benefits associated with services, we may be able to achieve meaningful biodiversity conservation at lower cost and with greater co-benefits

Nutritional Evaluation of Sago of Gebang Tree (Corypha utan Lamk) from Different Locations in West Timor - Indonesia for Broilers

Two experiments were conducted to evaluate the nutritional value of sago from different locations in West Timor, Indonesia for broilers. Experiment I aimed at determining the apparent metabolizable energy (AME) and nutrient digestibility of sago from different locations. A total of 120 broilers (unsexed, age 21 d) were randomly distributed to 24 metabolic cages (5 birds/cage). The experimental design was a completely randomized design (CRD) consisting of 6 treatments and 4 replications.  The experimental diets were a basal diet (maize-soy) and 5 treatment diets which were a mixture of basal ration (75%) and sago (25%) from different locations. Experiment II was about performance trials. Two different basal diets were formulated, supplemented with synbiotics and fed to 200 birds (unsexed, 10 birds/pen). The experimental design was a 2 x 2 factorial CRD. With the exception of phytate and phenol contents, the results showed that the location affected (p<0.05 to 0.01) the contents of dry matter, crude protein, and crude fiber, tannins, NDF, ADF, flavonoids, AME/n, and starch digestibility of sago. The location did not affect (p>0.05) ash, crude fat, starch, Ca, P, and gross energy contents of sago. Basal diets affected (p<0.05 to 0.001) all performance traits. Except for BWG, synbiotics did not affect (p>0.05) the performance of the birds. In conclusion, the nutrient composition and digestibility of sago are affected by locations. Sago is rich in starch and high in AME values, but poor sources of calcium, phosphor, and protein. Sago contains fiber, tannin, phytate, flavonoids, and phenol. Sago diets improved the performance of broilers. Synbiotics did not improve the performance of birds

STUDI DESKRIPTIF KETERAMPILAN GURU DALAM MEMBERIKAN PENGUATAN NON VERBAL PADA PEMBELAJARAN IPS DI KELAS VB SD NEGERI 05 KOTA BENGKULU

Penelitian ini bertujuan untuk mendeskripsikan keterampilan guru dalam memberikan penguatan non verbal pada pembelajaran IPS di kelas VB SD Negeri 05 Kota Bengkulu. Jenis penelitian yang digunakan adalah kualitatif deskriptif. Subjek penelitian adalah guru kelas VB SD Negeri 05 Kota Bengkulu. Teknik pengumpulan data menggunakan observasi dan wawancara. Uji keabsahan data melalui perpanjagan pengamatan, peningkatan ketekunan dan triangulasi. Teknik analisis data yang digunakan melalui reduksi data, penyajian data, dan penarikan kesimpulan. Hasil penelitian menunjukan bahwa: 1) Penguatan berupa mimik dan gerakan badan pada pembelajaran telah menerapkan tiga indikator yaitu penguatan berupa senyuman, anggukan kepala, dan ancungan jempol setiap sub indikator masing-masing terlihat guru telah melaksanakan dalam proses pembelajaran IPS. 2) Penguatan dengan cara mendekati telah menerapkan tiga indikator yaitu berupa berdiri di samping siswa, berjalan menuju siswa, dan berjalan di sisi, setiap sub indikator masing-masing sudah terlihat guru melaksanakan dalam proses pembelajaran IPS. 3) Penguatan berupa simbol atau benda dapat berupa memberikan komentar secara tertulis dan lisan kepada siswa, setiap sub masing-masing sudah terlihat namun masih ada beberapa pertemuan yang belum dilaksanakan guru pada pertemuan ketiga. Kesimpulan penelitian ini guru terlihat menguasai menerapkan keterampilan guru dalam memberikan penguatan non verbal pada pembelajaran IPS