Prediction of methionine oxidation risk in monoclonal antibodies using a machine learning method

ABSTRACT

Monoclonal antibodies (mAbs) have become a major class of protein therapeutics that target a spectrum of diseases ranging from cancers to infectious diseases. Similar to any protein molecule, mAbs are susceptible to chemical modifications during the manufacturing process, long-term storage, and in vivo circulation that can impair their potency. One such modification is the oxidation of methionine residues. Chemical modifications that occur in the complementarity-determining regions (CDRs) of mAbs can lead to the abrogation of antigen binding and reduce the drug’s potency and efficacy. Thus, it is highly desirable to identify and eliminate any chemically unstable residues in the CDRs during the therapeutic antibody discovery process. To provide increased throughput over experimental methods, we extracted features from the mAbs’ sequences, structures, and dynamics, used random forests to identify important features and develop a quantitative and highly predictive in silico methionine oxidation model.     

Cyclopaldic Acid,Seiridin, and Sphaeropsidin A as Fungal Phytotoxins,and Larvicidal and Biting Deterrents against Aedes aegypti (Diptera: Culicidae): Structure?Activity Relationships

Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. From a preliminary screening of fungal phytotoxins, cyclopaldic acid ( 1 ), seiridin ( 2 ), sphaeropsidin A ( 4 ), and papyracillic acid ( 5 ) were evaluated for their biting deterrent and larvicidal activities against Ae. aegypti L. Because compounds 1, 2, 4 , and 5 exhibited mosquito biting deterrent activities and 1 and 4 demonstrated larvicidal activities, further structure? activity relationship studies were initiated on these toxins. In biting‐deterrence bioassays, 1, 2, 4 , and 5 , 3,8‐didansylhydrazone of cyclopaldic acid, 1F , 5‐azidopentanoate of cyclopaldic acid A, 1G , the reduced derivative of cyclopaldic acid, 1 H , isoseiridin ( 3 ), 2′‐O‐acetylseiridin ( 2A ), 2′‐oxoseiridin ( 2C ), 6‐O‐acetylsphaeropsidin A ( 4A ), 8,14‐methylensphaeropsidin A methyl ester ( 4B ), and sphaeropsidin B ( 4C ) showed activities higher than the solvent control. Sphaeropsidin B ( 4C ) was the most active compound followed by 2A , while the other compounds were less active. Biting‐deterrence activity of compound 4C was statistically similar to DEET. In the larvicidal screening bioassays, only compounds 1 and 4 demonstrated larvicidal activities. Based on LD₅₀ values, compound 4 (LD₅₀ 36.8 ppm) was significantly more active than compound 1 (LD₅₀ 58.2 ppm). However, the activity of these compounds was significantly lower than permethrin.     

TAXONOMIC BIBLIOGRAPHY OF VASCULAR AQUATIC PLANTS IN SOUTHERN AFRICA

SUMMARY

The length mass relationship for a Labeo capensis population is described by the equation M = 0,0134 L^2'999 where 2,999 represents a constant the value of which indicates isometric growth. There is very little difference between the length/mass relationship for males and that for females and this is similar to the results found by Mulder (1973) for L. capensis in the Vaal River. The length/mass relationships for gravid males and females are different from that of the population as a whole indicating that maturity does result in a change of the body form which is in accordance with the results of Mulder (1973).

A modified formula to take into account, small length intervals of an age group, is used to calculate the relative condition factor for Labeo capensis from the Caledon River for a consecutive “winter” and “summer” period. The results show that the conhd1t10ni for Labeo capensis of the 0⁺, 1⁺ and 2⁺ age groups is better in the summer period than in the winter period, whereas in the older age groups 3⁺ to 5⁺ the condition in winter is better than in summer. This can be attributed to the attainment of sexual maturity at the age of 3⁺ years and the presence of large quantities of fat deposited in the body during the winter months, which are then utilised for the development of the gonads prior to spawning. These results are similar to those obtained for the same species by Mulder (1973) in the Vaal River and by Bloemhof (1974) in the Hardap Dam.     

Synthesis,Characterization, and Anti‐Amoebic Activity of N‐(Pyrimidin‐2‐yl)benzenesulfonamide Derivatives

A new series of N‐(pyrimidin‐2‐yl)benzenesulfonamide derivatives, 3a – 3i and 4a – 4i , was synthesized from pyrimidin‐2‐amines, 2a – 2i , with the aim to explore their effects on in vitro growth of Entamoeba histolytica. The chemical structures of the compounds were elucidated by elemental analysis, FT‐IR, ¹H‐ and ¹³C‐NMR, and ESI mass‐spectral data. In vitro anti‐amoebic activity was evaluated against HM1 : IMSS strain of Entamoeba histolytica. The IC₅₀ values were calculated by using the double dilution method. The results were compared with the IC₅₀ value of the standard drug ‘metronidazole’. The selected compounds were tested for their cytotoxic activities by cell‐viability assay using H9C2 cardiac myoblasts cell line, and the results indicated that all the compounds displayed remarkable >80% viabilities to a concentration of 100 μg/ml.     

38份晾晒烟种质资源遗传关系的SSR分析

利用SSR标记技术对38份晾晒烟种质资源的遗传关系进行了分析。从自己开发的近3000对烟草SSR引物中随机选出30对引物,在38份供试材料中共检测出173个等位基因,每对SSR引物可检测的等位基因数为2~11个,平均为5.77个。38份材料间遗传相似系数（GS）的变化范围为0.165-0.928,平均GS 为0.546。表明38份晾晒烟的遗传多样性丰富,遗传差异较大,亲缘关系较远。聚类分析表明,在L1（GS-0.165）处可将38个品种分为2大类,即晾晒烟类群和美国从烟草起源地收集的烟草（TI：Tobacco Instruction）类群;晾晒烟类群又可进一步分为4组,其聚类结果与所期望的结果基本一致。表明SSR是一种有效、稳定和可靠的分子标记,能较好地从分子水平上揭示烟草(尤其是晾晒烟)种质资源的遗传背景和亲缘关系。     

Seed dispersal networks in tropical forest fragments: Area effects,remnant species,and interaction diversity

Seed dispersal interactions involve key ecological processes in tropical forests that help to maintain ecosystem functioning. Yet this functionality may be threatened by increasing habitat loss, defaunation, and fragmentation. However, generalist species, and their interactions, can benefit from the habitat change caused by human disturbance while more specialized interactions mostly disappear. Therefore, changes in the structure of the local, within fragment, networks can be expected. Here we investigated how the structure of seed dispersal networks changes along a gradient of increasing habitat fragmentation. We analyzed 16 bird seed dispersal assemblages from forest fragments of a biodiversity-rich ecosystem. We found significant species–, interaction–, and network–area relationships, yet the later was determined by the number of species remaining in each community. The number of frugivorous bird and plant species, their interactions, and the number of links per species decreases as area is lost in the fragmented landscape. In contrast, network nestedness has a negative relationship with fragment area, suggesting an increasing generalization of the network structure in the gradient of fragmentation. Network specialization was not significantly affected by area, indicating that some network properties may be invariant to disturbance. Still, the local extinction of partner species, paralleled by a loss of interactions and specialist–specialist bird–plant seed dispersal associations, suggests the functional homogenization of the system as area is lost. Our study provides empirical evidence for network–area relationships driven by the presence/absence of remnant species and the interactions they perform.     

Effect of fungi–termite interaction on the chlorophyll content of three rice varieties grown on ultisol soil of Ikenne,south-west Nigeria

The effect of fungi–termite interaction on three rice varieties was conducted in a screen house at the Africa Rice Center (AfricaRice) Ibadan, Nigeria. Of the 10 fungi species (Fusarium verticilloides, Trichoderma sp., Aspergillus niger, Aspergillus flavus, Macrophoma sp., Neurospora sp., Botryodiplodia theobromae, Penicillum sp., Rhizopus sp. and Sclerotium rolfsii) isolated from termites, soil and rice plants, F. verticilloides, Trichoderma sp. and B. theobromae were used for the interaction study. Each fungus was inoculated singly and in combinations with termite into the root of each rice variety in potted soil. Leaf samples were taken to measure the chlorophyll content which is a major parameter to estimate effect of termite–fungi interaction. The chlorophyll content of the inoculated rice plants was significantly reduced when compared with the control. Fungi interaction with termite had significant reduction on the chlorophyll content. The synergistic relationship between the fungi and the termite was discussed.     

Beliefs Underlying Dog Owners' Health Care Behaviors: Results from a Large,Self-Selected,Internet Sample

ABSTRACT

Various behaviors must be performed by owners to promote good health for their dogs. The aim in this study was to use the results of an online survey, completed by 1,016 self-selected, Australian dog owners, to investigate relationships between demographic factors, beliefs, dog–owner relationship variables, and the performance of health-promoting behaviors. Specific behaviors examined included the provision of annual vaccinations and health checkups by a veterinarian, regular grooming and exercise, and the provision of a nutritionally balanced diet. Reported compliance was high in the self-selected sample, ranging between 77.8% for annual vaccinations and 98.8% for the provision of a nutritious diet. Regression analyses revealed that all of the behaviors we measured could be predicted from beliefs relating to health care practices and dog–owner relationship variables independently of demographic factors. The extent of dog and owner interactions, as well as the extent to which owners perceived important others to be supportive of the behaviors, emerged as particularly important variables. These statistically robust findings have implications for campaigns encouraging pet health promotion by owners.     

The Relationship between Empathy,Perception of Pain and Attitudes toward Pets among Norwegian Dog Owners

ABSTRACT

Anthropomorphism, attachment level, and belief in animal mind, as well as owners' level of empathy and attitudes toward their pets, are some of the factors that affect human–animal interactions. Owners' ability to identify painful conditions in their pets may have important consequences for the welfare of these animals. In addition to characterizing the typical Norwegian dog owner, the aim of this work was to study the relationship between empathy, attitudes, and perceived animal pain. A sample of 3,413 dog owners in Norway received an internet-based questionnaire (QuestBack?), to which1896 responded. The questionnaire included four parts: demographics, the Pet Attitude Scale (PAS), the Animal Empathy Scale (AES), and the Pain Assessment Instrument (PAI). For the PAI, participants were presented with 17 photos, showing dogs experiencing painful situations of varying degrees, and were asked to rate the level of pain they believed each animal was enduring, using a Visual Analogue Scale (VAS). Results showed that Norwegian dog owners had very high levels of animal-directed empathy and equally high levels of positive attitudes toward pets. There were differences based on gender, childhood pet keeping, income and education. Differences were also found rooted in owners' use of their dog, whether kept for companionship or hunting, as well as household size, an indication of human social relations. A strong, positive correlation (r = 0.58) was found between animal-directed empathy and positive attitudes toward pets. Empathy was found to be the best predictor of how people rated pain in dogs. The correlations were, however, moderate, indicating that other processes are also involved when observing animals in pain.