Force spectroscopy in studying infection

Biophysical force spectroscopy tools - for example optical tweezers, magnetic tweezers, atomic force microscopy, - have been used to study elastic, mechanical, conformational and dynamic properties of single biological specimens from single proteins to whole cells to reveal information not accessible by ensemble average methods such as X-ray crystallography, mass spectroscopy, gel electrophoresis and so on. Here we review the application of these tools on a range of infection-related questions from antibody-inhibited protein processivity to virus-cell adhesion. In each case we focus on how the instrumental design tailored to the biological system in question translates into the functionality suitable for that particular study. The unique insights that force spectroscopy has gained to complement knowledge learned through population averaging techniques in interrogating biomolecular details prove to be instrumental in therapeutic innovations such as those in structure-based drug design

Explaining the human resource management preferences of employees: A study of Chinese workers

The forces of globalization, technology and the differences or similarities in institutional systems place substantial pressure on convergence and divergence in HRM practices. Moreover, local customs and the responses from employees also pose serious constraints on the degree of convergence or divergence (Rowley and Benson 2002). In other words, there is what might be termed an upward influence coming from the employees. Although companies may benchmark HRM ‘best practices’, the actual adoption and success of these practices depends, to a large extent, on perceptions and acceptance from employees. However, the opinions of non-managerial employees have been largely neglected in the studies of HRM (Cooke 2009; Legge 1995; Guest 2002; Edgar and Geare 2005; Qiao, Khilji and Wang 2009). Cooke (2009), after reviewing studies on HRM in China published between 1998 and 2007 in major business and management journals, reported that two-thirds of the studies had collected data from managers and most of them relied on managers as the sole source for information. Since the information has mainly been provided by managers, there is the potential for bias because feedback from the managers probably reflects the ideal or ‘best practices’ of HRM that those managers want to implement, rather than the actual HR policies or practices being used in the organization. Thus Cooke (2009, p.19) argued that ‘unless we can broaden our research catchment to include views from the widest range of stakeholders, particularly the employees, our understanding of HRM in China remains partial, from management’s lens’. This study explores the HR preferences of Chinese employees, both non-managerial and managerial ones, based on a sample of 2852 questionnaires from companies in China. A number of questions are explored. For example, what do they think of a ‘promotion-from-within’ policy? Do they prefer an individual-based bonus or a group-based bonus? Do they prefer a ‘downward performance appraisal method’ or a ‘multi-source performance appraisal method’? The research findings shows a strong ‘group orientation’ and a great emphasis on ‘soft factors’ such as seniority, loyalty and connections in many HRM areas. The debate on whether Chinese HRM will converge or diverge towards the Western models is still ongoing. Many argue that there could be further convergence towards the Western practices because globalization may place substantial pressure on firms to standardize practices and policies (see Chen, Lawler and Bae 2005). Others argue that HRM is highly context specific in which institutional and cultural forces have enduring influences (see Rowley and Cooke 2010), which indicates a divergent perspective. The third group supports a ‘cross-vergence’ view which argues that there will be signs of convergence in certain areas but Chinese HRM will keep its ‘Chinese characteristics’ (Cooke 2005, 2010; Yeung, Warner and Rowley 2008; Warner 2009a, b). This study supports the ‘cross-vergence’ perspective. It is argued that certain areas of Chinese HRM are converging to the Western model, but the influence of traditional Chinese personnel practices remains strong. A ‘group orientation’, a major emphasis on ‘soft factors’ and a trade union presence is likely to remain as the three main features of Chinese HRM in the long-term

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death

Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisΔRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective