Max Weber in the thought of Edward Shils (1910–1995) and Ernest Gellner (1925–1995): the paradox of two Weberian approaches to the understanding of nations and nationalism?

This article traces the paradoxical impact of Weber's oeuvre on two major scholars of nationalism, Ernest Gellner and Edward Shils. Both these scholars died in 1995, leaving behind a rich corpus of writings on the nation and nationalism, much of which was inspired by Max Weber. The paradox is that although neither scholar accepted Weber's sceptical attitude to the concept of ‘nation’, they both used his other major concepts, such as ‘rationality’, ‘disenchantment’, ‘unintended consequences’, the ‘ethic of responsibility’ and ‘charisma’, in their very analyses of the nation and nationalism. And they both saw, each in his own way, the nation and nationalism as constitutive elements of modern societies. However, the paradox ceases being a paradox if one sees the integration, by Shils and Gellner, of concepts of the nation and of nationalism in the analysis of modernity, as a development of Weber's ideas.     

Dimensional characteristics of the Filipino dentition

This study concerns odontometric analysis of the Tagalog Filipinos in Manila, Philippines. Mesiodistal and buccolingual dimensions of the permanent dentition, a total of 56 variables, were studied in 100 males and 152 females. Results showed that their absolute tooth size was small. Relative tooth size, however, seemed to reflect their Southeast Asian Mongoloid origin. From univariate analysis, considerable male-female differences were shown in most of the variables studied. When correlation effects among the teeth were held constant through multivariate analysis, male-female distance was found to be small and substantial overlapping of the two multivariate distributions was evident. Only four variables could be shown by stepwise discriminant analysis to contribute significantly to the distance. Even the mandibular canine, as the strongest discriminator, could only account for 16.4% of the total multivariate distance. These contrasting findings for sex dimorphism in a set of teeth taken singly and taken jointly indicate that there are factors other than the teeth themselves that are expected to play important roles in determining overall male-female size differences in the set of teeth, and that these differences may not be as clear-cut as univariate analysis suggests.     

Multimodal Measurements of Single-Molecule Dynamics Using FluoRBT

Single-molecule methods provide direct measurements of macromolecular dynamics, but are limited by the number of degrees of freedom that can be followed at one time. High-resolution rotor bead tracking (RBT) measures DNA torque, twist, and extension, and can be used to characterize the structural dynamics of DNA and diverse nucleoprotein complexes. Here, we extend RBT to enable simultaneous monitoring of additional degrees of freedom. Fluorescence-RBT (FluoRBT) combines magnetic tweezers, infrared evanescent scattering, and single-molecule FRET imaging, providing real-time multiparameter measurements of complex molecular processes. We demonstrate the capabilities of FluoRBT by conducting simultaneous measurements of extension and FRET during opening and closing of a DNA hairpin under tension, and by observing simultaneous changes in FRET and torque during a transition between right-handed B-form and left-handed Z-form DNA under controlled supercoiling. We discover unanticipated continuous changes in FRET with applied torque, and also show how FluoRBT can facilitate high-resolution FRET measurements of molecular states, by using a mechanical signal as an independent temporal reference for aligning and averaging noisy fluorescence data. By combining mechanical measurements of global DNA deformations with FRET measurements of local conformational changes, FluoRBT will enable multidimensional investigations of systems ranging from DNA structures to large macromolecular machines.     

Can some microbes promote host stress and benefit evolutionarily from this strategy?

Microbes can influence host physiology and behavior in many ways. Here we review evidence suggesting that some microbes can contribute to host stress (and other microbes can contribute to increased resilience to stress). We explain how certain microbes, which we call “stress microbes,” can potentially benefit evolutionarily from inducing stress in a host, gaining access to host resources that can help fuel rapid microbial replication by increasing glucose levels in the blood, increasing intestinal permeability, and suppressing the immune system. Other microbes, which we term “resilience microbes,” can potentially benefit from making hosts more resilient to stress. We hypothesize that “stress microbes” use a fast life history strategy involving greater host exploitation while “resilience microbes” use a slow life history strategy characterized by more aligned evolutionary interests with the host. In this paper, we review the evidence that microbes affect host stress and explain the evolutionary pressures that could lead microbes to manipulate host stress, discuss the physiological mechanisms that are known to be involved in both stress and microbial activity, and provide some testable predictions that follow from this hypothesis.     

Active site plasticity of endonuclease V from Salmonella typhimurium

Base deamination is a major type of DNA damage under nitrosative stress. Endonuclease V initiates repair of deaminated base damage by making a nucleolytic incision one nucleotide away from the 3' side of the lesion. Within the endonuclease V family, the substrate specificities are different from one enzyme to another. In this study, we investigated deamination lesion cleavage activities of endonuclease V from the macrophage-residing pathogen, Salmonella typhimurium. Salmonella endonuclease V exhibits limited turnover on cleavage of deoxyinosine- and xanthosine-containing DNA. Binding analysis indicates that this single-turnover property is caused by tight binding to nicked products. The nicking activity is similar between the double-stranded deoxyinosine- and deoxyxanthosine-containing DNA. Cleavage rates are not affected by bases opposite the deoxyinosine or deoxyxanthosine lesions. The enzyme is also active on single-stranded deoxyinosine- and deoxyxanthosine-containing DNA. Unlike endonuclease V from Thermotoga maritima, Salmonella endonucleae V can only turnover deoxyuridine-containing DNA to a limited extent when substrate is in excess. Binding analysis indicates that Salmonella endonuclease V achieves tight binding to deoxyuridine-containing DNA, a property that distinguishes it from Thermotoga endonuclease V. Cleavage analysis on mismatch-containing DNA also indicates that the active site of Salmonella endonuclease V can accommodate pyrimidine-containing mismatches, resulting in more comparable cleavage of pyrimidine- and purine-containing mismatches. This comprehensive DNA cleavage and binding analysis reveals the plastic nature in the active site of Salmonella endonuclease V, which allows the enzyme to enfold both purine and pyrimidine deaminated lesions or base pair mismatches.     

Identification of a novel miRNA that increases transient protein expression in combination with valproic acid

Transient gene expression in mammalian cells is an efficient process to produce recombinant proteins for various research applications and large molecule therapeutics development. For the first time, we report a screen to identify human microRNAs (miRNAs) that increase titers after polyethylenimine (PEI) mediated transient transfection of a HEK293 cell line. From a library of 875 miRNAs, we identified 2 miRNAs, miR‐26a‐5p and miR‐337‐5p, that increased human IgG1 (huIgG1) yields by 50 and 25%, respectively. The titer increase was achievable by expressing miR‐26a‐5p from oligonucleotides or a plasmid. Furthermore, combining miR‐26a‐5p with valproic acid (VPA) treatment doubled huIgG1 titers. Assessment of miR‐26a‐5p and VPA treatment across a panel of 32 human and murine antibodies demonstrates that the level of yield enhancement was molecule‐dependent, with most exhibiting a range of 50–100% titer increase. These findings exemplify that combining genetic and chemical manipulation can be an effective strategy to enhance transient transfection productivity. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1139–1145, 2017     

Dissecting the senescence-like program in tumor cells activated by Ras signaling

Activated Ras signaling can induce a permanent growth arrest in osteosarcoma cells. Here, we report that a senescence-like growth inhibition is also achieved in human carcinoma cells upon the transduction of H-Ras(V12). Ras-induced tumor senescence can be recapitulated by the transduction of activated, but not wild-type, MEK. The ability for H-Ras(V12) to suppress tumor cell growth is drastically compromised in cells that harbor endogenous activating ras mutations. Notably, growth inhibition of tumor cells containing ras mutations can be achieved through the introduction of activated MEK. Tumor senescence induced by Ras signaling can occur in the absence of p16 or Rb and is not interrupted by the inactivation of Rb, p107, or p130 via short hairpin RNA or the transduction with HPV16 E7. In contrast, inactivation of p21 via short hairpin RNA disrupts Ras-induced tumor senescence. In summary, this study uncovers a senescence-like program activated by Ras signaling to inhibit cancer cell growth. This program appears to be intact in cancer cells that do not harbor ras mutations. Moreover, cancer cells that carry ras mutations remain susceptible to tumor senescence induced by activated MEK. These novel findings can potentially lead to the development of innovative cancer intervention.