Tick-borne Thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product Mx1

We show that tick-transmitted Thogoto virus is sensitive to interferon- induced nuclear Mx1 protein, which is known for its specific antiviral action against orthomyxoviruses. Influenza virus-susceptible BALB/c mice (lacking a functional Mx1 gene) developed severe disease symptoms and died within days after intracerebral or intraperitoneal infection with a lethal challenge dose of Thogoto virus. In contrast, Mx1-positive congenic, influenza virus- resistant BALB·A2G-Mx1 mice remained healthy and survived. Likewise, A2G, congenic B6·A2G-Mx1 and CBA·T9-Mx1 mice (derived from influenza virus- resistant wild mice) as well as Mx1-transgenic 979 mice proved to be resistant. Peritoneal macrophages and interferon-treated embryo cells from resistant mice exhibited the same resistance phenotype in vitro. Moreover, stable lines of transfected mouse 3T3 cells that constitutively express Mx1 protein showed increased resistance to Thogoto virus infection. We conclude that an Mx1-sensitive step has been conserved during evolution of orthomyxoviruses and suggest that the Mx1 gene in rodents may serve to combat infections by influenza virus-like arboviruses.</p

Short incubation periods of atypical H-type BSE in cattle with EK211 and KK211 prion protein genotypes after intracranial inoculation

In 2006, a case of atypical H-type BSE (H-BSE) was found to be associated with a germline mutation in the PRNP gene that resulted in a lysine substitution for glutamic acid at codon 211 (E211K). The E211K amino acid substitution in cattle is analogous to E200K in humans, which is associated with the development of genetic Creutzfeldt-Jakob disease (CJD). In the present study, we aimed to determine the effect of the EK211 prion protein genotype on incubation time in cattle inoculated with the agent of H-BSE; to characterize the molecular profile of H-BSE in KK211 and EK211 genotype cattle; and to assess the influence of serial passage on BSE strain. Eight cattle, representing three PRNP genotype groups (EE211, EK211, and KK211), were intracranially inoculated with the agent of H-BSE originating from either a case in a cow with the EE211 prion protein genotype or a case in a cow with E211K amino acid substitution. All inoculated animals developed clinical disease; post-mortem samples were collected, and prion disease was confirmed through enzyme immunoassay, anti-PrPSc immunohistochemistry, and western blot. Western blot molecular analysis revealed distinct patterns in a steer with KK211 H-BSE compared to EK211 and EE211 cattle. Incubation periods were significantly shorter in cattle with the EK211 and KK211 genotypes compared to the EE211 genotype. Inoculum type did not significantly influence the incubation period. This study demonstrates a shorter incubation period for H-BSE in cattle with the K211 genotype in both the homozygous and heterozygous forms

Twenty-four Hour Holter Monitoring in Finishing Cattle Housed Outdoors

Ambulatory electrocardiogram monitoring, in the form of Holter monitoring, has been used in human and veterinary medicine for decades as an aid in the diagnosis and determination of appropriate therapy of heart rhythm disturbances. Within veterinary medicine, Holter monitors have been primarily used in companion animal species, yet little attention has been given to food animal species. Moreover, the heart rhythm in clinically normal cattle fed high concentrate diets and housed outdoors in confined drylot facilities has not been previously reported. In order to properly identify pathologic arrhythmias in cattle, the normal rhythm and arrhythmia prevalence in healthy cattle should be defined. Most prior reports of arrhythmia in cattle have been recordings of relatively shorter duration and in animals that were hospitalized or being handled for various reasons. Therefore, the objective of this study was to determine normal Holter monitor registrations including heart rate, rhythm, number of ventricular premature complexes, and atrial premature complexes in unrestrained finishing Angus steers

Can becoming a leader change your personality? An investigation with two longitudinal studies from a role-based perspective

Organizational research has predominantly adopted the classic dispositional perspective to understand the importance of personality traits in shaping work outcomes. However, the burgeoning literature in personality psychology has documented that personality traits, although relatively stable, are able to develop throughout one’s whole adulthood. A crucial force driving adult personality development is transition into novel work roles. In this article, we introduce a dynamic, role-based perspective on the adaptive nature of personality during the transition from the role of employee to that of leader (i.e., leadership emergence). We argue that during such role transitions, individuals will experience increases in job role demands, a crucial manifestation of role expectations, which in turn may foster growth in conscientiousness and emotional stability. We tested these hypotheses in two 3-wave longitudinal studies using a quasi-experimental design. We compared the personality development of 2 groups of individuals (1 group promoted from employees into leadership roles and the other remaining as employees over time), matched via the propensity score matching approach. The convergent results of latent growth curve modeling from the 2 studies support our hypotheses regarding the relationship between becoming a leader and subsequent small, but substantial increases in conscientiousness over time and the mediating role of job role demands. The relationship between becoming a leader and change of emotional stability was not significant. This research showcases the prominence of examining and cultivating personality development for organizational research and practice

Demonstration of asymmetric electron conduction in pseudosymmetrical photosynthetic reaction centre proteins in an electrical circuit

Photosynthetic reaction centres show promise for biomolecular electronics as nanoscale solar-powered batteries and molecular diodes that are amenable to atomic-level re-engineering. In this work the mechanism of electron conduction across the highly tractable Rhodobacter sphaeroides reaction centre is characterized by conductive atomic force micro-scopy. We find, using engineered proteins of known structure, that only one of the two cofactor wires connecting the positive and negative termini of this reaction centre is capable of conducting unidirectional current under a suitably oriented bias, irrespective of the magnitude of the bias or the applied force at the tunnelling junction. This behaviour, strong functional asymmetry in a largely symmetrical protein–cofactor matrix, recapitulates the strong functional asymmetry characteristic of natural photochemical charge separation, but it is surprising given that the stimulus for electron flow is simply an externally applied bias. Reasons for the electrical resistance displayed by the so-called B-wire of cofactors are explored

The native architecture of a photosynthetic membrane

In photosynthesis, the harvesting of solar energy and its subsequent conversion into a stable charge separation are dependent upon an interconnected macromolecular network of membrane-associated chlorophyll–protein complexes. Although the detailed structure of each complex has been determined, the size and organization of this network are unknown. Here we show the use of atomic force microscopy to directly reveal a native bacterial photosynthetic membrane. This first view of any multi-component membrane shows the relative positions and associations of the photosynthetic complexes and reveals crucial new features of the organization of the network: we found that the membrane is divided into specialized domains each with a different network organization and in which one type of complex predominates. Two types of organization were found for the peripheral light-harvesting LH2 complex. In the first, groups of 10–20 molecules of LH2 form light-capture domains that interconnect linear arrays of dimers of core reaction centre (RC)–light-harvesting 1 (RC–LH1–PufX) complexes; in the second they were found outside these arrays in larger clusters. The LH1 complex is ideally positioned to function as an energy collection hub, temporarily storing it before transfer to the RC where photochemistry occurs: the elegant economy of the photosynthetic membrane is demonstrated by the close packing of these linear arrays, which are often only separated by narrow 'energy conduits' of LH2 just two or three complexes wide

Новые языковые реальности употребления претерита в немецком гипотаксисе

Целью статьи являются обобщение и теоретическое обоснование нового употребления претерита в относительном значении в конкретных видах придаточных предложений с презенсом в главном предложении. В статье анализируются коннотативные нюансы относительного значения претерита, регулярность замены префекта-пассива и перфекта именного составного сказуемого с глаголом "sein" на претеритальные формы в гипотаксисе, а также особое место претерита в системе немецких временных форм.Метою статті є узагальнення та теоретичне обґрунтування нового вживання претериту у релятивному значенні у конкретних видах сурядно-підрядних речень з презентом у сурядному реченні. У статті подано аналіз конототивні нюанси претериту і регулярність зміни перфекту пасиву та іменного присудка з дієсловом "sein" на претеритальні форми у гіпотаксису, а також особливе місце претериту у системі німецьких часових форм.The article aims at generalization and theoretical Explanation of modern preterit usage in relative meaning in certain types of clauses, with the Present tense in the main clause. The article deals with the analysis of connotative component meanings of the relative preterit and the regularity of substitution of preterit forms in hypotaxes for the passive perfect tense and the perfect form of the nominal compound predicate with the verb 'sein' as well as the specificity of preterit in the system of German tenses

CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer

Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit the access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA tumor microenvironment promote concomitant chemotherapy delivery and increased antineoplastic response in murine models of PDA. Prior studies could not determine whether chemotherapy delivery or microenvironment modulation per se were the dominant features in treatment response, and such information could guide the optimal translation of these preclinical findings to patients. To distinguish between these possibilities, we used a chemical inhibitor of cytidine deaminase to stabilize and thereby artificially elevate gemcitabine levels in murine PDA tumors without disrupting the tumor microenvironment. Additionally, we used the FG-3019 monoclonal antibody (mAb) that is directed against the pleiotropic matricellular signaling protein connective tissue growth factor (CTGF/CCN2). Inhibition of cytidine deaminase raised the levels of activated gemcitabine within PDA tumors without stimulating neoplastic cell killing or decreasing the growth of tumors, whereas FG-3019 increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. The response to FG-3019 correlated with the decreased expression of a previously described promoter of PDA chemotherapy resistance, the X-linked inhibitor of apoptosis protein. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models, and by extension in PDA patients