The phenotype and tissue-specific nature of multipotent cells derived from human mature adipocytes

Dedifferentiated fat (DFAT) cells derived from mature adipocytes have been considered to be a homogeneous group of multipotent cells, which present to be an alternative source of adult stem cells for regenerative medicine. However, many aspects of the cellular nature about DFAT cells remained unclarified. This study aimed to elucidate the basic characteristics of DFAT cells underlying their functions and differentiation potentials. By modified ceiling culture technique, DFAT cells were converted from human mature adipocytes from the human buccal fat pads. Flow cytometry analysis revealed that those derived cells were a homogeneous population of CD13⁺ CD29⁺ CD105⁺ CD44⁺ CD31⁻ CD34⁻ CD309⁻ α-SMA⁻ cells. DFAT cells in this study demonstrated tissue-specific differentiation properties with strong adipogenic but much weaker osteogenic capacity. Neither did they express endothelial markers under angiogenic induction.     

Ozone pollution influences soil carbon and nitrogen sequestration and aggregate composition in paddy soils

Background and aims

Much attention has focused on the effects of tropospheric ozone (O₃) on terrestrial ecosystems and plant growth. Since O₃ pollution is currently an issue in China and many parts of the world, understanding the effects of elevated O₃ on soil carbon (C) and nitrogen (N) sequestration is essential for efforts to predict C and N cycles in terrestrial ecosystems under predicted increases in O₃. Thus the main objective of this study was to determine whether an increases in atmospheric O₃ concentration influenced soil organic C (SOC) and N sequestration.

Methods

A free-air O₃ enrichment (O₃-FACE) experiment was started in 2007 and used continuous O₃ exposure from March to November each year during crop growth stage in a rice (Oryza sativa L.)—wheat (Triticum aestivum L.) rotation field in the Jiangsu Province, China. We investigated differences in SOC and N and soil aggregate composition in both elevated and ambient O₃ conditions.

Results

Elevated atmospheric O₃ (18–80 nmol mol^?1 or 50 % above the ambient) decreased the SOC and N concentration in the 0–20 cm soil layer after 5 years. Elevated O₃ significantly decreased the SOC concentration by 17 % and 5.6 % in the 0–3 cm and the 10–20 cm layers, respectively. Elevated O₃ significantly decreased the N concentration by 8.2–27.8 % in three layers at the 20 cm depth. In addition, elevated O₃ influenced the formation and transformation of soil aggregates and the distribution of SOC and N in the aggregates across soil layer classes. Elevated O₃ significantly decreased the macro-sized aggregate fraction (16.8 %) and associated C and N (0.5 g kg^?1 and 0.32 g kg^?1, respectively), and significantly increased the silt+ clay-sized aggregate fraction (61 %) and associated C (1.7 g kg^?1) in the 0–3 cm layer. Elevated O₃ significantly decreased the macro-sized aggregate fraction (9.6 %) and associated C and N (1.4 g kg^?1 and 0.35 g kg^?1, respectively), and significantly increased the silt+ clay-sized aggregate fraction (41.8 %) and decreased the corresponding associated N (0.14 g kg^?1) in the 3–10 cm layer. Elevated O₃ did not significantly effect the formation and transformation of aggregates in the 10–20 cm layer, yet it did significantly increase the C concentration in the macro-sized fraction (1 g kg^?1) and decrease the N concentration in the macro- and micro-sized fractions (0.24 g kg^?1 and 0.16 g kg^?1, respectively).

Conclusion

Long-term exposure to elevated atmospheric O₃ negatively affected the physical structure of the soil and impaired soil C and N sequestration.     

The limited number of available nucleotide and protein sequencedata from the recent H7N9 cases in China impeded investigation and characterization of the outbreak

Dear Editor,Nucleotide and protein sequences of isolates collectedfrom infected populations can be useful for determiningthe threats,such as host adaptation,which are associatedwith the emergence of new lineages.March 2013 saw thefirst reports of a new H7N9 lineage in Shanghai,Chinathat saw a gradual increase in the number of cases;but,by 17th May 2013,four Chinese provinces had ended     

Tolerability,pharmacokinetics and pharmacodynamics of CMAB007, a humanized anti-immunoglobulin E monoclonal antibody,in healthy Chinese subjects

The goal of the studies presented here was to determine the tolerability, pharmacokinetic and pharmacodynamic profiles of CMAB007, a biosimilar of omalizumab (Xolair; a humanized anti-immunoglobulin E monoclonal antibody), in healthy, male Chinese subjects. Thirty-six healthy Chinese men participated in two open-label, dose-escalation studies: 27 in a single-dose study (150, 300 or 600 mg) and 9 in a multiple-dose study (150 or 300 mg every 4 weeks for 20 weeks). The safety profiles of both studies were generally unremarkable. No drug-related adverse event was observed. CMAB007 exhibited a linear PK profile over the dose range of 150-600 mg. In the single-dose study, maximum concentration (C_max) was reached within 6–8 d, and C_max and area under concentration-time curve (AUC) increased linearly with the dose. In the multiple-dose study, steady-state appeared to have been achieved after the third dose. C_ss-max and AUC_τ also showed dose-linearity. A dose-dependent suppression of free IgE was observed during treatment, as a median percentage change from baseline, 91.9–98.8%, in the three single-dose groups. No anti-CMAB007 antibodies were detected after dosing in any subject. Subcutaneous administration of CMAB007 was well-tolerated and seemed to be effective in reducing free IgE in healthy Chinese volunteers, which provides important information for further clinical studies.Key words: pharmacokinetics, pharmacodynamics, safety, IgE, humanized antibody     

Intermittent preventive treatment of malaria in children: a qualitative study of community perceptions and recommendations in Burkina Faso and Mali

Background

Intermittent preventive treatment of malaria in children (IPTc) is a highly efficacious method of malaria control where malaria transmission is highly seasonal. However, no studies published to date have examined community perceptions of IPTc.

Methods

A qualitative study was undertaken in parallel with a double-blind, placebo-controlled, randomized trial of IPTc conducted in Mali and Burkina Faso in 2008–2009 to assess community perceptions of and recommendations for IPTc. Caregivers and community health workers (CHWs) were purposively sampled. Seventy-two in-depth individual interviews and 23 focus group discussions were conducted.

Findings

Widespread perceptions of health benefits for children led to enthusiasm for the trial and for IPTc specifically. Trust in and respect for those providing the tablets and a sense of obligation to the community to participate in sanctioned activities favoured initial adoption. IPTc fits in well with existing understandings of childhood illness. Participants did not express concerns about the specific drugs used for IPTc or about providing tablets to children without symptoms of malaria. There was no evidence that IPTc was perceived as a substitute for bed net usage, nor did it inhibit care seeking. Participants recommended that distribution be “closer to the population”, but expressed concern over caregivers'' ability to administer tablets at home.

Conclusions

The trial context mediated perceptions of IPTc. Nonetheless, the results indicate that community perceptions of IPTc in the settings studied were largely favourable and that the delivery strategy rather than the tablets themselves presented the main areas of concern for caregivers and CHWs. The study identifies a number of key questions to consider in planning an IPTc distribution strategy. Single-dose formulations could increase the success of IPTc implementation, as could integration of IPTc within a package of activities, such as bed net distribution and free curative care, for which demand is already high.     

Development of a humanized HLA-A2.1/DP4 transgenic mouse model and the use of this model to map HLA-DP4-restricted epitopes of HBV envelope protein

A new homozygous humanized transgenic mouse strain, HLA-A2.1(+/+)HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAβ(-/-)β2m(-/-) (HLA-A2/DP4), was obtained by crossing the previously characterized HLA-A2(+/+)β2m(-/-) (A2) mouse and our previously created HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAβ(-/-) (DP4) mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present study demonstrated that HLA-A2/DP4 transgenic mice can faithfully mimic human cellular responses. Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal model carrying alleles present to more than a quarter of the human population. This model should facilitate the identification of novel HLA-A2- and HLA-DP4-restricted epitopes and vaccine development as well as the characterization of HLA-DP4-restricted responses against infection in humans.     

Application of hypoiodite-mediated aminyl radical cyclization to synthesis of solasodine acetate

Solasodine acetate, an anticancer steroidal alkaloid, was synthesized from diosgenin in 8 steps with an overall yield of 23%. A key synthetic step involves the formation of 5/6-oxazaspiroketal moiety via hypoiodite-mediated aminyl radical cyclization of a steroidal primary amine.     

Promotion of spinosad biosynthesis by chromosomal integration of the Vitreoscilla hemoglobin gene in Saccharopolyspora spinosa

To promote spinosad biosynthesis by improving the limited oxygen supply during high-density fermentation of Saccharopolyspora spinosa, the open reading frame of the Vitreoscilla hemoglobin gene was placed under the control of the promoter for the erythromycin resistance gene by splicing using overlapping extension PCR. This was cloned into the integrating vector pSET152, yielding the Vitreoscilla hemoglobin gene expression plasmid pSET152EVHB. This was then introduced into S. spinosa SP06081 by conjugal transfer, and integrated into the chromosome by site-specific recombination at the integration site ΦC31 on pSET152EVHB. The resultant conjugant, S. spinosa S078-1101, was genetically stable. The integration was further confirmed by PCR and Southern blotting analysis. A carbon monoxide differential spectrum assay showed that active Vitreoscilla hemoglobin was successfully expressed in S. spinosa S078-1101. Fermentation results revealed that expression of the Vitreoscilla hemoglobin gene significantly promoted spinosad biosynthesis under normal oxygen and moderately oxygen-limiting conditions (P<0.01). These findings demonstrate that integrating expression of the Vitreoscilla hemoglobin gene improves oxygen uptake and is an effective means for the genetic improvement of S. spinosa fermentation.