Middle Eocene habitat shifts in the North American western interior: A case study

There has been great interest in the global warming events that heralded the onset of the Eocene and particularly the response of mammalian faunas to these events. However, little information is available on the subsequent deterioration of tropical habitats in the interior of North America after these major warming episodes. The decline of tropical habitats is thought to have begun during the middle Eocene in the interior of North America, but until now, no studies have been able to document the details of this event. Recent fossil collection and stratigraphic studies from sites in southwestern Wyoming and northeastern Utah that span the middle Eocene offer a unique opportunity to evaluate changes in habitat in the western interior. Using a discriminant function analysis, habitats were reconstructed for a sequence of eight stratigraphically controlled middle Eocene assemblages. Adaptive profiles (diets, substrate use, and body masses) of fossil mammal communities were statistically compared to those of extant faunas from a variety of Neotropical habitats. Previously published magnetostratigraphic data from Utah provided a means to correlate our stratigraphic sections to the geomagnetic polarity time scale and the oxygen isotope record. The discriminant model shows that there was a significant change in the mammalian community ecology near the end of the late middle Eocene that is likely reflective of a habitat shift. When correlated to the time scale and oxygen isotope record, this key transition from forested habitats typical of the tropical early Eocene to more open woodlands began about 42 million years ago in this region of the Rocky Mountains.     

A Novel L-ficolin/Mannose-binding Lectin Chimeric Molecule with Enhanced Activity against Ebola Virus

Ebola viruses constitute a newly emerging public threat because they cause rapidly fatal hemorrhagic fevers for which no treatment exists, and they can be manipulated as bioweapons. We targeted conserved N-glycosylated carbohydrate ligands on viral envelope surfaces using novel immune therapies. Mannose-binding lectin (MBL) and L-ficolin (L-FCN) were selected because they function as opsonins and activate complement. Given that MBL has a complex quaternary structure unsuitable for large scale cost-effective production, we sought to develop a less complex chimeric fusion protein with similar ligand recognition and enhanced effector functions. We tested recombinant human MBL and three L-FCN/MBL variants that contained the MBL carbohydrate recognition domain and varying lengths of the L-FCN collagenous domain. Non-reduced chimeric proteins formed predominantly nona- and dodecameric oligomers, whereas recombinant human MBL formed octadecameric and larger oligomers. Surface plasmon resonance revealed that L-FCN/MBL76 had the highest binding affinities for N-acetylglucosamine-bovine serum albumin and mannan. The same chimeric protein displayed superior complement C4 cleavage and binding to calreticulin (cC1qR), a putative receptor for MBL. L-FCN/MBL76 reduced infection by wild type Ebola virus Zaire significantly greater than the other molecules. Tapping mode atomic force microscopy revealed that L-FCN/MBL76 was significantly less tall than the other molecules despite similar polypeptide lengths. We propose that alterations in the quaternary structure of L-FCN/MBL76 resulted in greater flexibility in the collagenous or neck region. Similarly, a more pliable molecule might enhance cooperativity between the carbohydrate recognition domains and their cognate ligands, complement activation, and calreticulin binding dynamics. L-FCN/MBL chimeric proteins should be considered as potential novel therapeutics.     

生物软件在序列分析过程中的运用

介绍了组合使用BLAST、FASTA/BLASTScan3.2,或用多序列比对软件,从数据库中快速提取大数量目标序列,最后用MEGA4快捷编辑整理大数量序列的方法。还介绍了一种生成核酸序列与其氨基酸序列相似性百分率整合表格的方法。简述了对引物设计的基本认识并介绍了多重引物兼容性筛选软件;对构建系统发育树的认识并引出分子进化树构建软件MEGA4的使用和PAUP 4.0常用建树命令模块。期望这些方法和软件的使用能解决生物序列分析过程的常见问题。     

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Introduction

The human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.

Methods

This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.

Results

Adalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).

Conclusions

An allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.     

FADS2 Polymorphisms Modify the Effect of Breastfeeding on Child IQ

Background

Breastfeeding is important for child cognitive development. A study by Caspi et al has suggested that rs174575 within the FADS2 gene moderates this effect so that children homozygous in the minor allele (GG genotype) have similar IQs irrespective of feeding method.

Methods and Principal Findings

In our study of 5934 children aged 8 years, no genetic main effect with IQ was found for rs174575. However, an interaction with this polymorphism was observed such that breastfed GG children performed better than their formula fed counterparts by an additional 5.8 points [1.4, 10.1] (interaction p = 0.0091). Interaction results were attenuated by about 10% after adjustment for 7 factors. This study also investigated rs1535, another FADS2 polymorphism in linkage disequilibrium with rs174575, together with performance and verbal IQ, finding similar results although effect sizes were generally reduced.

Conclusions and Significance

This study did not replicate the findings of Caspi et al. In contrast to their study, GG children exhibited the greatest difference between feeding methods such that breastfed children performed similarly irrespective of child genotype whereas formula fed GG children performed worse than other children on formula milk. Further studies are required to replicate these findings.     

Evidence that Soil Carbon Pool Determines Susceptibility of Semi-Natural Ecosystems to Elevated Nitrogen Leaching

Deposition of reactive nitrogen (N) compounds has the potential to cause severe damage to sensitive soils and waters, but the process of ‘nitrogen saturation’ is difficult to demonstrate or predict. This study compares outputs from a simple carbon–nitrogen model with observations of (1) regional- and catchment-scale relationships between surface water nitrate and dissolved organic carbon (DOC), as an indicator of catchment carbon (C) pool; (2) inter-regional variations in soil C/N ratios; and (3) plot scale soil and leachate response to long-term N additions, for a range of UK moorlands. Results suggest that the simple model applied can effectively reproduce observed patterns, and that organic soil C stores provide a critical control on catchment susceptibility to enhanced N leaching, leading to high spatial variability in the extent and severity of current damage within regions of relatively uniform deposition. Results also support the hypothesis that the N richness of organic soils, expressed as C/N ratio, provides an effective indicator of soil susceptibility to enhanced N leaching. The extent to which current C/N is influenced by N deposition, as opposed to factors such as climate and vegetation type, cannot be unequivocally determined on the basis of spatial data. However, N addition experiments at moorland sites have shown a reduction in organic soil C/N. A full understanding of the mechanisms of N-enrichment of soils and waters is essential to the assessment of current sensitivity to, and prediction of future damage from, globally increasing reactive nitrogen deposition.     

Changes in nucleolar morphology and proteins during infection with the coronavirus infectious bronchitis virus

The nucleolus is a dynamic subnuclear structure involved in ribosome subunit biogenesis, cell cycle control and mediating responses to cell stress, among other functions. While many different viruses target proteins to the nucleolus and recruit nucleolar proteins to facilitate virus replication, the effect of infection on the nucleolus in terms of morphology and protein content is unknown. Previously we have shown that the coronavirus nucleocapsid protein will localize to the nucleolus. In this study, using the avian infectious bronchitis coronavirus, we have shown that virus infection results in a number of changes to the nucleolus both in terms of gross morphology and protein content. Using confocal microscopy coupled with fluorescent labelled nucleolar marker proteins we observed changes in the morphology of the nucleolus including an enlarged fibrillar centre. We found that the tumour suppressor protein, p53, which localizes normally to the nucleus and nucleolus, was redistributed predominately to the cytoplasm.     

Infection of mice with aerosolized Mycobacterium tuberculosis: use of a nose-only apparatus for delivery of low doses of inocula and design of an ultrasafe facility

Aerosolized delivery of virulent or hypervirulent Mycobacterium tuberculosis requires careful consideration of methodology and safety. To maximize safety, we installed a nose-only aerosol apparatus that can reproducibly deliver a low dose (<100 CFU per mouse) of M. tuberculosis in a carefully designed biohazard facility.