Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor

HIV's considerable capacity to vary its HLA-I-restricted peptide antigens allows it to escape from host cytotoxic T lymphocytes (CTLs). Nevertheless, therapeutics able to target HLA-I-associated antigens, with specificity for the spectrum of preferred CTL escape mutants, could prove effective. Here we use phage display to isolate and enhance a T-cell antigen receptor (TCR) originating from a CTL line derived from an infected person and specific for the immunodominant HLA-A(*)02-restricted, HIVgag-specific peptide SLYNTVATL (SL9). High-affinity (K(D) < 400 pM) TCRs were produced that bound with a half-life in excess of 2.5 h, retained specificity, targeted HIV-infected cells and recognized all common escape variants of this epitope. CD8 T cells transduced with this supraphysiologic TCR produced a greater range of soluble factors and more interleukin-2 than those transduced with natural SL9-specific TCR, and they effectively controlled wild-type and mutant strains of HIV at effector-to-target ratios that could be achieved by T-cell therapy.     

Denitrification rate determined by nitrate disappearance is higher than determined by nitrous oxide production with acetylene blockage

A mixed beech and spruce forest soil was incubated under potential denitrification assay (PDA) condition with 10% acetylene (C₂H₂) in the headspace of soil slurry bottles. Nitrous oxide (N₂O) concentration in the headspace, as well as nitrate, nitrite and ammonium concentrations in the soil slurries were monitored during the incubation. Results show that nitrate disappearance rate was higher than N₂O production rate with C₂H₂ blockage during the incubation. Sum of nitrate, nitrite, and N₂O with C₂H₂ blockage could not recover the original soil nitrate content, showing an N imbalance in such a closed incubation system. Changes in nitrite and ammonium concentration during the incubation could not account for the observed faster nitrate disappearance rate and the N imbalance. Non-determined nitric oxide (NO) and N₂ production could be the major cause, and the associated mechanisms could vary for different treatments. Commonly applied PDA measurement likely underestimates the nitrate removal capacity of a system. Incubation time and organic matter/nitrate ratio are the most critical factors to consider using C₂H₂ inhibition technique to quantify denitrification. By comparing the treatments with and without an antibiotic, the results suggest that microbial N uptake probably played a minor role in N balance, and other denitrifying enzymes but nitrate reductase could be substantially synthesized during the incubation.     

DIFFERENTIAL EFFECTS OF SEDIMENTS ON SURVIVAL AND GROWTH OF FUCUS SERRATUS EMBRYOS (FUCALES,PHAEOPHYCEAE)1

Recruitment of seaweeds through small reproductive stages is limited on sediment inundated rocky shores and largely unsuccessful in soft sediment environments. Burial in sediment has several potentially negative effects for seaweed propagules, and these effects were differentiated in a laboratory experiment. We investigated how light deprivation, sediment type (grain size, organic content, and origin), and sediment chemistry (oxygen presence and toxicity through hydrogen sulfide) affected survivorship and growth of Fucus serratus L. embryos. Presence of hydrogen sulfide had overriding negative impacts on both survivorship and growth of Fucus embryos, independently of sediment type and light availability. In contrast, simple anaerobiosis generally did not impair survival or growth of the embryos. Fine sediments, 3 mm thick, significantly reduced embryo survivorship, presumably through accumulation of metabolic waste products in the immediate vicinity of the embryos as a consequence of constrained diffusion. This effect was equally pronounced in the presence of a 1‐mm layer of organically rich biodeposits. Irradiance levels did not affect survival of embryos but influenced growth. Decreasing thickness and increasing coarseness of sediments together represented a gradient of enhanced light penetration and diffusion. Growth of embryos increased along this gradient. In nature, soft sediment environments with organically enriched muds (e.g. tidal flats and salt marshes) represent habitats least favorable for colonization through small reproductive stages of seaweeds.     

Pteropus lylei primarily forages in residential areas in Kandal,Cambodia

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In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B

Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug.     

Use of a genetically engineered protein for the design of a multivalent MRI contrast agent

The majority of clinically used contrast agents (CAs) for magnetic resonance imaging have low relaxivities and thus require high concentrations for signal enhancement. Research has turned to multivalent, macromolecular CAs to increase CA efficiency. However, previously developed macromolecular CAs do not provide high relaxivities, have limited biocompatibility, and/or do not have a structure that is readily modifiable to tailor to particular applications. We report a new family of multivalent, biomacromolecular, genetically engineered protein polymer-based CAs; the protein backbone contains evenly spaced lysines that are derivatized with gadolinium (Gd(III)) chelators. The protein's length and repeating amino acid sequence are genetically specified. We reproducibly obtained conjugates with an average of 8-9 Gd(III) chelators per protein. These multivalent CAs reproducibly provide a high relaxivity of 7.3 mM (-1) s (-1) per Gd(III) and 62.6 mM (-1) s (-1) per molecule. Furthermore, they can be incorporated into biomaterial hydrogels via chemical cross-linking of the remaining free lysines, and provide a dramatic contrast enhancement. Thus, these protein polymer CAs could be a useful tool for following the evolution of tissue engineering scaffolds.     

农田和森林土壤中氧化亚氮的产生与还原

采用土壤淤浆方法对丹麦农田和山毛榉森林土壤反硝化过程中Ｎ２Ｏ的产生与还原进行了研究。同时考察了硝酸根和铵离子对反硝化作用的影响。结果表明,森林土壤反硝化活性大于农田土壤,但农田土壤中Ｎ２Ｏ还原活性大于森林土壤,表现在农田和森林土壤中Ｎ２Ｏ／Ｎ２的产生比率分别为０．１１和３．６５。硝酸根和铵离子能促进两种土壤中的Ｎ２Ｏ产生,但可降低农田土壤中的Ｎ２Ｏ还原速率,与农田土壤相比,硝酸根可降低森林土壤Ｎ２     

Overview of dengue outbreaks in the southwestern Indian Ocean and analysis of factors involved in the shift toward endemicity in Reunion Island: A systematic review

BackgroundDengue is the world’s most prevalent mosquito-borne viral disease. It is endemic in many tropical and subtropical countries and represents a significant global health burden. The first reports of dengue virus (DENV) circulation in the South West Indian Ocean (SWIO) islands date back to the early 1940s; however, an increase in DENV circulation has been reported in the SWIO in recent years. The aim of this review is to trace the history of DENV in the SWIO islands using available records from the Comoros, Madagascar, Mauritius, Mayotte, Seychelles, and Reunion. We focus in particular on the most extensive data from Reunion Island, highlighting factors that may explain the observed increasing incidence, and the potential shift from one-off outbreaks to endemic dengue transmission.MethodsFollowing the PRISMA guidelines, the literature review focused queried different databases using the keywords “dengue” or “Aedes albopictus” combined with each of the following SWIO islands the Comoros, Madagascar, Mauritius, Mayotte, Seychelles, and Reunion. We also compiled case report data for dengue in Mayotte and Reunion in collaboration with the regional public health agencies in these French territories. References and data were discarded when original sources were not identified. We examined reports of climatic, anthropogenic, and mosquito-related factors that may influence the maintenance of dengue transmission independently of case importation linked to travel.Findings and conclusionsThe first report of dengue circulation in the SWIO was documented in 1943 in the Comoros. Then not until an outbreak in 1976 to 1977 that affected approximately 80% of the population of the Seychelles. DENV was also reported in 1977 to 1978 in Reunion with an estimate of nearly 30% of the population infected. In the following 40-year period, DENV circulation was qualified as interepidemic with sporadic cases. However, in recent years, the region has experienced uninterrupted DENV transmission at elevated incidence. Since 2017, Reunion witnessed the cocirculation of 3 serotypes (DENV-1, DENV-2 and DENV-3) and an increased number of cases with severe forms and deaths. Reinforced molecular and serological identification of DENV serotypes and genotypes circulating in the SWIO as well as vector control strategies is necessary to protect exposed human populations and limit the spread of dengue.     

Theorie der Protoplasma- und Muskelbewegung

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