The relative toxicity of a spore preparation of Bacillus thuringiensis var. israelensis against fourth instar larvae of Aedes aegypti and Toxorhynchites amboinensis: suspension feeding compared with enemas and forced feeding

The toxic effect of a spore preparation of Bacillus thuringiensis var. israelensis Berliner Serotype H-14 (Bti) on 4th instar larvae of Aedes aegypti L. and Toxorhynchites amboinensis (Doleschall) was observed when given either in a suspension feeding test or when injected orally as a forced feeding or via the anus as an enema. The A. aegypti larvae showed the greater sensitivity to Bti both because they greatly concentrate the toxin by filter feeding and they are more sensitive to Bti than are the larvae of T. amboinensis. The latter appeared approximately two-fold less sensitive to Bti than the former after taking into account their greater body weight.

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Résumé La toxicité sur des larves de 4ème stade de A. aegypti et T. amboinensis, d'une préparation de spores de B. thuringiensis var. israelensis Berliner sérotype H-14, a été examinée après: injection orale par alimentation forcée, injection anale comme lavement, — le témoin étant une alimentation à partir d'une suspension de spores.Les larves de A. aegypti ont présenté la plus grande sensibilité au Bti d'une part parce qu'elles concentrent beaucoup la toxine avec leur alimentation par filtration, et parce qu'elles sont plus sensibles sensu stricto au Bti. Même en tenant compte de leur poids plus élevé, T. amboinensis est apparu comme deux fois moins sensible au Bti.

     

Behavior of bonobos (Pan paniscus) following their capture of monkeys in Zaire

For the first time, three cases of capture and forced interaction were observed between bonobos (Pan paniscus)and two other species of primates (Colobus angolensisand Cercopithecus ascanius)in the Lilungu (Ikela) region, Republic of Zaire. The bonobos interacted with the captured primates as if they were dealing with individuals of their own species. They sought cooperation in their interactions with the captured young primates without scccess. There is no evidence that they ate the captives.     

Developability studies before initiation of process development

Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2−8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples. We present here three case studies reflecting three typical outcomes: (1) no major or unexpected degradation is found and the study results are used to inform early identification of degradation pathways and potential critical quality attributes within the Quality by Design framework defined by US Food and Drug Administration guidance documents; (2) identification of specific degradation pathway(s) that do not affect potency of the molecule, with subsequent definition of proper process control and formulation strategies; and (3) identification of degradation that affects potency, resulting in program termination and reallocation of resources.     

Artificial selection on sexual aggression: Correlated traits and possible trade-offs

Forced copulation is an extreme form of sexual aggression that can affect the evolution of sex-specific anatomy, morphology, and behavior. To characterize mechanistic and evolutionary aspects of forced copulation, we artificially selected male fruit flies based on their ability to succeed in the naturally prevalent behavior of forced matings with newly eclosed (teneral) females. The low and high forced copulation lineages showed rapid divergence, with the high lineages ultimately showing twice the rates of forced copulation as the low lineages. While males from the high lineages spent more time aggressively pursuing and mounting teneral females, their behavior toward non-teneral and heterospecific females was similar to that of males from the low lineages. Males from the low and high lineages also showed similar levels of male-male aggression. This suggests little or no genetic correlations between sexual aggression and non-aggressive pursuit of females, and between male aggression toward females and males. Surprisingly however, males from the high lineages had twice as high mating success than males from the low lineages when allowed to compete for consensual mating with mature females. In further experiments, we found no evidence for trade-offs associated with high forced mating rates: males from the high lineages did not have lower longevity than males from the low lineages when housed with females, and four generations of relaxed selection did not lead to convergence in forced mating rates. Our data indicate complex interactions among forced copulation success and consensual mating behavior, which we hope to clarify in future genomic work.     

SNV and haplotype analysis reveals new CSRP1 variants associated with growth and carcass traits

The cysteine and glycine-rich protein 1 and 2 genes (CSRP1 and CSRP2) are an effective growth factor in promoting skeletal muscle growth in vitro and vivo. However, in cattle, the information on the CSRP1 and CSRP2 genes is very limited. The aim of this study was to examine the association of the CSRP1 and CSRP2 variants with growth and carcass traits in cattle breeds. Three single nucleotide variants (SNVs) were identified within the bovine CSRP1 gene, whereas CSRP2 gene has not detected any SNVs, using DNA pooled sequencing, PCR-RFLP, and forced PCR-RFLP methods. These SNVs include g. 801T>C (Intron 2), g. 46T>C (Exon 3) and g. 99C>G (Intron 3). Besides, we also investigated haplotype frequencies and linkage disequilibrium (LD) coefficients for three SNVs in all study populations. LD and haplotype structure of CSRP1 were different between breeds. The result of haplotype analysis demonstrated eight haplotype present in QC (Qinchuan) and one haplotype in CH (Chinese Holstein). Only haplotype 1 (TTC), shared by all two populations, comprised 10.74% and 100.00%, of all haplotypes observed in QC and CH, respectively. Haplotype 5 (CTC) had the highest haplotype frequencies in QC (30.98%) and haplotype 1 had the highest haplotype frequencies in CH (100.00%). The statistical analyses indicated that one single SNV and 19 combined haplotypes were significantly or highly significantly associated with growth and carcass traits in the QC cattle population (P < 0.05 or P < 0.01). Quantitative real-time PCR (qRT-PCR) analyses showed that the bovine CSRP1 and CSRP2 genes were widely expressed in many tissues. The results of this study suggest that the CSRP1 gene possibly is a strong candidate gene that affects growth and carcass traits in the Chinese beef cattle breeding.     

Enhancement of exercise endurance capacity by fermented deer antler in BALB/c mice

To investigate the activity of fermented deer antler on exercise endurance capacity, we evaluated endurance capacity in five-week-old male BALB/c mice by administering the fermented deer antler extract (FA) or the non-fermented deer antler extract (NFA) and then subjected the mice to exercise in the form of swimming. The mice administered 500?mg/kg/day of FA showed a significant increase in swimming time compared with mice administered placebo (16.55?min vs. 21.64?min, P?<?0.05). Serum lactate dehydrogenase (LDH), the marker of the liver and muscle damage, was significantly lower in FA groups. However, NFA groups did not show significantly different swimming time or serum LDH from that of the control group. Moreover, the FA-500 group had significantly higher hepatic superoxide dismutase (SOD) activity after forced swimming than the control and NFA groups (P?<?0.05). These findings suggest that fermentation may increase the exercise endurance capacity of the deer antler.     

蛋白类药物强制降解研究进展

强制降解试验可以揭示药物可能的降解途径,为蛋白类药物制剂组方的开发、储存、运输提供支持,因此,强制降解研究在蛋白类药物研发中具有重要作用,但目前关于强制条件的选择、作用时间和降解程度尚无标准指南。综述了目前常用的强制降解条件（高温、pH、氧化、光照、反复冻融和震荡或搅拌）及不同强制降解条件对蛋白类药物的影响,并提出了相关设计建议,以期为蛋白类药物的强制降解试验条件的选择提供参考。     

Enhancement of antidepressant potency by a potentiator of AMPA receptors

1. AMPA receptor potentiators (ARPs) exhibit antidepressant-like activity in preclinical tests (for example, the forced swim test) that are highly predictive of efficacy in humans. Unlike most currently used antidepressants, ARPs do not elevate extracellular levels of biogenic amines (e.g., 5HT, NE) in prefrontal cortex at doses that are active in the forced swim test.2. The present series of experiments examined the effects of combining the ARP, LY 392098, with biogenic amine-based antidepressants in the forced swim test. Male, NIH Swiss mice were placed in a cylinder of water and observed for attempted escape behaviors and immobility.3. LY 392098 dose-dependently decreased immobility as did a range of classical antidepressants. At doses of LY 392098 below those that decreased immobility, this compound significantly increased the potency with which fluoxetine and citalopram (SSRI antidepressants), imipramine (tricyclic antidepressant), duoxetine (norepinephrine/serotonin uptake blocker), nisoxetine (norepinephrine uptake inhibitor), and rolipram (PDE4 inhibitor) decreased immobility in the forced swim test with potency shifts upward of 5-fold (fluoxetine, imipramine, and rolipram). Likewise, ineffective doses of the traditional antidepressants potentiated the effects LY 392098 with shifts in the dose-effect functions that were 10-fold or more for citalopram, fluoxetine, imipramine, and duloxetine.4. Combined with other evidence for a role of AMPA receptors in the efficacy of antidepressants, the current data suggest that the addition of an ARP may augment the activity and perhaps the onset of the therapeutic effects of biogenic amine and second messenger-based antidepressants.