Efficient, chemoselective synthesis of immunomicelles using single-domain antibodies with a C-terminal thioester

Background  

Classical bioconjugation strategies for generating antibody-functionalized nanoparticles are non-specific and typically result in heterogeneous compounds that can be compromised in activity. Expression systems based on self-cleavable intein domains allow the generation of recombinant proteins with a C-terminal thioester, providing a unique handle for site-specific conjugation using native chemical ligation (NCL). However, current methods to generate antibody fragments with C-terminal thioesters require cumbersome refolding procedures, effectively preventing application of NCL for antibody-mediated targeting and molecular imaging.     

Ultrasound enhanced prehospital thrombolysis using microbubbles infusion in patients with acute ST elevation myocardial infarction: Rationale and design of the Sonolysis study

Background

The CONSORT Statement provides recommendations for reporting randomized controlled trials. We assessed the extent to which leading medical journals that publish reports of randomized trials incorporate the CONSORT recommendations into their journal and editorial processes.

Methods

This article reports on two observational studies. Study 1: We examined the online version of 'Instructions to Authors' for 165 high impact factor medical journals and extracted all text mentioning the CONSORT Statement or CONSORT extension papers. Any mention of the International Committee of Medical Journal Editors (ICMJE) or clinical trial registration were also sought and extracted. Study 2: We surveyed the editor-in-chief, or editorial office, for each of the 165 journals about their journal's endorsement of CONSORT recommendations and its incorporation into their editorial and peer-review processes.

Results

Study 1: Thirty-eight percent (62/165) of journals mentioned the CONSORT Statement in their online 'Instructions to Authors'; of these 37% (23/62) stated this was a requirement, 63% (39/62) were less clear in their recommendations. Very few journals mentioned the CONSORT extension papers. Journals that referred to CONSORT were more likely to refer to ICMJE guidelines (RR 2.16; 95% CI 1.51 to 3.08) and clinical trial registration (RR 3.67; 95% CI 2.36 to 5.71) than those journals which did not. Study 2: Thirty-nine percent (64/165) of journals responded to the on-line survey, the majority were journal editors. Eighty-eight percent (50/57) of journals recommended authors comply with the CONSORT Statement; 62% (35/56) said they would require this. Forty-one percent (22/53) reported incorporating CONSORT into their peer-review process and 47% (25/53) into their editorial process. Eighty-one percent (47/58) reported including CONSORT in their 'Instructions to Authors' although there was some inconsistency when cross checking information on the journal's website. Sixty-nine percent (31/45) of journals recommended authors comply with the CONSORT extension for cluster trials, 60% (27/45) for harms and 42% (19/45) for non-inferiority and equivalence trials. Few journals mentioned these extensions in their 'Instructions to Authors'.

Conclusion

Journals should be more explicit in their recommendations and expectations of authors regarding the CONSORT Statement and related CONSORT extensions papers.     

Survival of <Emphasis Type="Italic">Listeria monocytogenes</Emphasis> in Wilted and Additive-Treated Grass Silage

Grass was field-dried to 3 different dry matter (DM) levels (200, 430 and 540 g/kg) and inoculated with 10⁶–10⁷ cfu/g of a Listeria monocytogenes strain sharing a phagovar occasionally involved in food-borne outbreaks of listeriosis. Formic acid (3 ml/kg) or lactic acid bacteria (8·10⁵/g) with cellulolytic enzymes were applied only to forages with low and intermediate DM levels. Forages were ensiled in laboratory silos (1700 ml) and were stored at 25°C for 30 or 90 days. After 90 days of storage, L. monocytogenes could not be detected in any silo, except one with the high dry matter grass without additive. After 30 days of storage, between 10² and 10⁶ cfu L. monocytogenes/g silage were isolated from the untreated silages. Increasing the DM content from 200 to 540 g/kg did not reduce listeria counts possibly because of the lower production of fermentation acids (higher pH). In silages treated with additives, counts of L. monocytogenes were always lower than in silages without additive. In wet silages (DM 200 g/kg) both additives were effective, but in the wilted silages (DM 430 g/kg) only the bacterial additive reduced listeria counts below detection level. Listeria counts were highly correlated to silage pH (r = 0.92), the concentration of lactic acid (r = -0.80) and the pooled amount of undissociated acids (r = -0.83).     

Behavioral, cellular and molecular consequences of the dopamine transporter gene inactivation

Mice lacking the the plasma membrane dopamine transporter (DAT), following gene inactivation or knock out, show an increase in their spontaneous locomotor activity that is of the same magnitude than in normal mice treated with amphetamine or cocaine, known to increase levels of dopamine in the basal ganglia. Many adaptive responses have occurred in these animals than could not compensate for the hyper activity of the dopamine system. Surprisingly, while intracellular dopamine levels were of only 5%, extracellular dopamine levels were increased by 300%. We investigated the regulation of tyrosine hydroxylase (TH), the rate limiting enzyme of dopamine synthesis, and found that this enzyme is regulated at the levels of mRNA, protein, trafficking as well as in its regional, cellular and subcellular organization. Our results establish not only the central importance of the transporter as the key element controlling dopamine levels in the brain, but also its role in the behavioral and biochemical action of amphetamine, cocaine and morphine. In addition, these mice have provided key elements leading to possible clinical and social implications for illnesses such as Parkinson disease, attention deficit disorder and drug addiction.     

Evaluation of infestation percentage of cotton fields to the spiny bollworm,Earias insulana Boisduval (Lep.: Noctuidae), and its relationship with pheromone traps

Spiny bollworm, Earias insulana Boisduval (Lepidoptera: Noctuidae), is one of the most important pest of malvaceous plants throughout the world, except America. In recent years, this insect has been serious pest for cotton fields in southern regions of Iran, especially Darab region of Fars province. In order to evaluate the performance of sex pheromone in reduction of infestation percentage of the spiny bollworm by mass trapping method, an experiment was carried out during year of 2012 in Darab region in Randomised Completely Block Design with six treatments and four replications. The treatments were: application of the four sex pheromone trap densities at the rates of 16, 20, 24 and 30?traps/h, application of Larvin chemical insecticide at the rate of 1?L/h and control. Percentages of infected bolls and flowers to E. insulana were weekly determined. The application of Larvin insecticide performed as the pest population reached to economic threshold level. Analysis variance of results showed that there are significant differences between time, trap number and time?×?trap interaction on infestation percentage per hectare. During sampling time, the highest infestation percentage was in control treatment and the lowest one was observed in 30 and 24?traps/h treatments. The peak of infestation percentage was seen in 18th of November. The best efficiency among treatments was observed in pheromone trap. In conclusion, using sex pheromone trap in comparison to application of insecticides can efficiently reduce infestation level of cotton fields.     

室内条件下小菜蛾在五种花椰菜栽培种上的生物学和种群统计(英文)

【目的】小菜蛾Plutella xylostella (L.)是全球十字花科植物上最重要的害虫。由于施药成本的增加以及对环境的破坏性危害,抗性栽培种成为控制小菜蛾的理想选择。本研究中,鉴于对花椰菜不同栽培种的抗感性缺乏充分的了解,我们评价了几个常见栽培种的抗性以及不同植物栽培种对害虫种群增长潜力的影响。【方法】在25±2℃, RH 65%±5% 和光周期16L∶8D的室内条件下,研究了小菜蛾P. xylostella在5种花椰菜栽培种（Smilla, White cloud, Buris, Galiblanka 和Tokita）上的生命表参数。【结果】不小菜蛾幼期发育历期变化范围从Smilla上的13.44 d至Buris上的15.88 d。在Buris上观察到最高的生殖力。在Smilla上饲养的小菜蛾种群内禀增长率（0.27±0.02）和有限增长率（1.32±0.13）最高,而倍增时间最短（2.50 d）。【结论】因此,与其他栽培种相比,在伊朗南部Smilla更适合小菜蛾存活和繁殖,在条件合适和天敌缺乏时该害虫的种群能快速增长。