Retrovirus and filovirus “immunosuppressive motif” and the evolution of virus pathogenicity in HIV-1, HIV-2, and ebola viruses

The immunosuppressive motif was found to be present in the glycoproteins of retroviruses and filoviruses. This sequence is also conserved in the pathogenic lentiviruses, HIV-1 and SIV, and is absent from HIV-2 gp41 and from an apathogenic simian retrovirus. The present analysis deals with the possible involvement of the immunosuppresessive motif in the pathogenicity of retroviruses and filoviruses, and the reasons for the conservation of this motif. The ancestral gene from which the immunosuppressive motif originated is not known.     

Modularity and Intersection of “What”, “Where” and “How” Processing of Visual Stimuli: A New Method of fMRI Localization

Summary: Research on the modularity of perceptual and cognitive processes has often pointed to a ventral-dorsal distinction in cortical pathways that depend upon the nature of the stimuli and the task. However, it is not clear whether the dorsal, occipital-parietal stream specializes in locating visual objects (i.e., a “where” stream), or taking action toward objects (i.e., a “how” stream), although there is some consensus for a ventral, occipital-temporal “what” stream that specializes in the identification of visual objects. It is also not clear to what extent word and picture processing are modular along these streams, as functional imaging maps to date have not addressed the modularity question directly. Here we present two types of functional imaging maps that directly show modularity and intersection of processing function for word and picture stimuli in tasks that require decisions about “what is”, “where is”, or “how do you interact with” a stimulus (N=6 participants). Our results reveal a middle dorsal “how” stream with some modular regions of activation that are distinct from activation during “where” processing, and that words and pictures involve several modular regions of activation along these streams. This research was supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada in the form of grants to R.B. and G.E.S., and a post-doctoral fellowship to C.K.F, and by the Canadian Institutes for Health Research (CIHR) and the Saskatchewan Health Services Utilization and Research Commission (HSURC) in the form of grants to G.E.S. We thank Jennifer Hadley and Francis Shih for technical assistance.     

“Desmoplastic” versus “classic” medulloblastoma: Comparison of DNA content,histopathology and differentiation

Summary A microfluorometric analysis was performed to analyse the DNA content of 42 medulloblastomas (MBs) and to seek correlations, if any existed, between the DNA distribution and ploidy values, neoplasm types (i.e. classic vs desmoplastic), histological features of aggressiveness, and immunocytochemical features indicating glial and/or neuronal differentiation. Thirty-one cases were classified as classic and 11 cases as desmoplastic MBs. Ten of 11 desmoplastic MBs had a near-diploid main mode and the remaining 1 case had a near-tetraploid main mode. Moreover, 10 of 11 (90%) cases showed a monomodal DNA distribution diagram. All these cases showed a uniform histology. In contrast, classic MBs represented a heterogeneous group of neoplasms. Twenty-two cases were near-diploid, 5 cases were near-tetraploid and 3 cases were near-triploid. The histogram type distribution showed a similar heterogeneity. Twelve of 31 (39%) cases had a monomodal histogram, 12 (39%) cases had a bimodal diagram and 7 (22%) cases a complex DNA distribution. There was a statistically significant difference (P<0.001) in terms of prevalence of DNA monomodal histograms between classic and desmoplastic MBs. Significant correlations were not observed among classic MBs between histological features of aggresiveness, type and degree of differentiation and DNA distribution. The present study indicates that desmoplastic MBs represent a homogeneous group of neoplasms in terms of histology and DNA distribution. In contrast, classic MBs are lesions with different degrees of histologically apparent aggressiveness and a complex DNA distribution.     

Histologic, immunohistochemical, and ultrastructural findings in a case of minocycline-associated “black thyroid”

We report on a 37-yr-old woman with known antemortem ingestion of minocyclin who died suddenly from a ruptured cerebral aneurysm. At autopsy, her thyroid gland, although not enlarged, was diffusely black, caused by the deposition of a melanin-like pigment that stained positive with Schmorl’s reagent. The pigment could be bleached with permanganate, and on examination by electron microscopy, it appeared to be deposited within the thyrocyte lysosomes. Additional immunostaining with many antibodies revealed an increase in vimentin staining in the follicular epithelium compared with normal control thyroid glands. Staining for cytoplasmic thyroglobulin was markedly reduced, despite normal thyroid indices performed on stored antemortem blood. Stainable ubiquitin in the follicular epithelium appeared reduced compared with control thyroid tissues. These immunohistochemical findings may reflect disruptions of lysosomal transport and function associated with the abnormal accumulation of pigment. This appears to be the only case of minocyclin-associated “black thyroid” in which extensive immunohistochemical investigations have been performed.     

Slow potentials, event-related potentials, “gamma-band” activity, and motor responses during aversive conditioning in humans

We examined slow potentials, transient event-related potentials, and oscillatory-like responses in the electroencephalogram during aversive conditioning in humans, in order to determine what is happening in the neocortex when behavioral adaptations are learned. Pictures of an angry and a happy human face served as rein-forced (CS+) and unreinforced (CS-) conditioned stimu li, respectively, in one group, and either the reversed condition or two discriminably different neutral faces in two other groups (total n=48 subjects). The unconditioned stimulus (US) was intracutaneous shock delivered to the left hand 5 s after CS+ onset. The electroencephalographic (EEG) activity was recorded from Fz, Cz, Pz, C3, and C4, electromyographic (EMG) activity from bilateral forearm and corrugator muscles, and skin conductance from the right hand. During acquisition a negative slow potential developed after CS+ (not CS-), which was more pronounced when a neutral face served as CS+. Early (iCNV, initial contingent negative variation) and late (tCNV, terminal contingent negative variation) components of the slow-potential response were positively related to the magnitude of conditioned EMG responses. Differentiation of tCNV was larger when neutral faces signaled the US; iCNV persisted during extinction when a happy face served as CS+. Late-occurring event-related potentials (ERPs) elicited by the US diminished over conditioning, whereas short-latency US components and ERPs elicited by CS events did not. Fourier analysis revealed oscillatory (gamma-band) activity between 30 and 40 Hz, which persisted up to 3 s after US delivery and diminished as conditioning progressed. Our findings indicate that learning is expressed in neocortical structures at the earliest stages of conditioning. The functional roles of the three types of EEG response in learning are discussed.     

Genetic “Clocks” and “Soft” Events: A Twin Model for Pubertal Development and Other Recalled Sequences of Developmental Milestones, Transitions, or Ages at Onset

We propose and explore a twin model to examine the basis for synchrony that often characterizes different facets of normal development. In so doing we also present an approach to the analysis of soft events; events for which available reports of dates or ages of occurrence are unreliable or inconsistent. Discrepancies among reports are accounted for by a statistical measurement model. This combines current status error reflecting uncertain definition of onset and two mechanisms for the phenomenon of telescoping, namely, systematic compression of the time scale and heteroscedastic random measurement error. Statistically, the model can be viewed as a mixed generalized linear model with random effects within both mean and variance functions or, alternatively, as involving multiplicative random effects. We apply the model to multiple maternal reports on menarche and onset of breast development in twin daughters. Fitted to data from the Virginia Twin Study Of Adolescent and Behavioral Development by the use of penalized/predictive quasi-likelihood, the model provided much improved estimates of the true age-at-onset distribution as compared to those from a naive analysis. Results suggested that the observed variance was made up almost entirely of genetic variance and measurement error variance due to telescoping and current status errors and that the timing of breast development and menarche are largely under the control of a common set of genes. Results also indicated that maternal recollections of the onset of breast development were both more poorly defined and subject to greater recall errors than maternal recollections of menarche.     

Comment on “religiosity and United States suicide rates, 1972-1978”

This article comments on the Martin article on religiosity and suicide rates in the United States. Specifically, it is pointed out by the present author that Martin's data do not allow him to draw the conclusions that he offered in his article. A correlational study does not allow for cause and effect conclusions, and the use of group data precludes conclusions about individual cases.     

Immunological relationship between “ pathogenesis-related” leaf proteins from tomato,tobacco and cowpea

When tomato plants are infected with different pathogens an increase in the concentration of the “pathogenesis-related” (PR) protein p14 is observed in the acid-extractable leaf protein fraction. Antibodies were raised in rabbits against a purified preparation of this protein and used in Western blot analyses. It was found that the accumulation of p14 and two related proteins is due to an active response of the tomato plant to infection and not caused by the degradation of a preexisting leaf protein. The p14-antiserum cross-reacts with PR proteins from other solanaceous plant species such as the tobacco (Nicotiana tabacum) cultivars Samsun NN and Xanthi nc and Nicotiana glutinosa. It also cross-reacts with a PR protein from cowpea (Vigna unguiculata), which belongs to the unrelated family Leguminosae. This immunological relationship indicates that PR proteins of different plant species have structural features in common and it also suggests a possible similarity in their still unknown function.     

In-body optical stimulation formed connective tissue vascular grafts, “biotubes,” with many capillaries and elastic fibers

The autologous biotube, developed by using in-body tissue architecture technology, is one of the most promising small-diameter vascular grafts in regenerative medicine. The walls of the biotubes obtained by a traditional silicone mold-based method were very thin, and this is still the primary obstacle while handling anastomosis, even though these biotubes have adequate pressure resistance ability. This pilot study showed the effect of optical stimulation of subcutaneous tissue formation in the body during the preparation of the biotubes. A blue light-emitting diode (LED) was embedded into a silicone rod as a mold. The biotube was prepared by placing the luminescent molds into the dorsal subcutaneous pouches of a pair of beagles (each weighing ~10 kg) for 2 weeks under photoirradiation. The wall thickness of the obtained biotubes was 506.9 ± 185.7 μm, which was remarkably more than that of the previous biotubes prepared by 2 months of embedding similarly in beagles’ subcutaneous pouches (thickness, 77.2 ± 14.8 μm). Many capillaries with smooth muscle cells were infiltrated into the wall and concentrated in the internal layer. Interestingly, the formation of elastic fibers had already started along with collagen fibers, mostly with a regular circumferential orientation. The short-term in-body optical stimulation resulted in the rapid formation of a biotube. These phenomena will allow easy surgical handling and may induce vascular maturation in histology during the acute phase after implantation.     

“Under Pressure” – How fungi evade,exploit, and modulate cells of the innate immune system

The human immune system uses an arsenal of effector mechanisms to prevent and counteract infections. Yet, some fungal species are extremely successful as human pathogens, which can be attributed to a wide variety of strategies by which these fungi evade, exploit, and modulate the immune system. These fungal pathogens normally are either harmless commensals or environmental fungi. In this review we discuss how commensalism, but also life in an environmental niche without human contact, can drive the evolution of diverse and specialized immune evasion mechanisms. Correspondingly, we discuss the mechanisms contributing to the ability of these fungi to cause superficial to life-threatening infections.     

Antenatal screening and early intervention for “perinatal” distress, depression and anxiety: where to from here?

Summary Recent developments in the study of mental health issues surrounding childbirth, have brought about a shift from the narrow concept of postnatal depression (PND) to a consideration of the spectrum of depressive and anxiety disorders arising in the perinatal period – which in the mental health context is defined as encompassing pregnancy and the first year postpartum. This shift has been associated with a growing recognition of the potential for prevention and early intervention in the perinatal period.In this article, the difficulties of antenatal screening with the aim of predicting PND are highlighted and contrasted with the potential benefits of antenatal screening aimed at identifying psychological morbidity – whether pre-existing risk factors and/or current symptoms – which may have bearing across the entire perinatal period. The literature on randomized controlled trials of targeted antenatal interventions to reduce PND and indicated interventions in postnatally depressed women are also reviewed. Future clinical and research directions in the field of early intervention for perinatal mood and anxiety disorders are identified.     

“Harris Hematoxylin,” What Harris Really Wrote and the Mechanism of Hemalum Stains

Abstract

In current textbooks, Harris “hematoxylin” stain includes differentiation in acid alcohol, followed by bluing of sections. However, Harris (1900) did not mention differentiation, but strongly recommended progressive staining with an acidified or diluted solution of his formula or with Mayer's acid hemalum. A review of the chemistry of hematoxylin and hemalum stains showed binding of unoxidized hematoxylin by tissues. Oxidation of hematoxylin yields anionic hematein, which does not contain a quinonoid ring. Two hematein ions form a chelate with an Al⁺⁺⁺ cation. Hemalum is bound to tissues by coordinate and hydrogen bonds. Dye binding by nuclei occurs mainly via non-ionic bonding. Protons of acids added to the hemalum solution or used in differentiation compete with the metal for binding sites. When appropriate amounts of acid are added to the hemalum solution, nuclei are stained selectively. Acidified hemalum solutions require only two steps, staining and washing, and yield perfectly reproducible staining patterns, even in the hands of trainees. (The J Histotechnol 10:257, 1987.)     

Astrovirus-induced “white chicks” condition – field observation,virus detection and preliminary characterization

Chicken astrovirus (CAstV) was recently indicated as the factor of the “white chicks” condition associated not only with increased embryo/chick mortality but also with weakness and white plumage of hatched chicks. In February 2014, organ samples (livers and kidneys) from dead-in-shell embryos, as well as 1-day-old whitish and normal chicks, were delivered from one hatchery in Poland for disease diagnosis. The samples originated from the same 30-week-old breeder flock in which the only observed abnormal signs were 4–5% decrease in the number of hatched chickens and the presence (about 1%) of weaker chicks with characteristic whitish plumage among normal ones. CAstV was detected in submitted samples and was then isolated in 10-day-old embryonated specific pathogen free (SPF) chicken eggs. We also reproduced an infection model for the “white chicks” condition in SPF layer chickens using the isolated PL/G059/2014 strain as the infectious agent. Results of experimental reproduction of the “white chicks” condition were somewhat more serious than field observation. The administration of the CAstV material into the yolk sac of 8-day-old SPF chicken eggs caused delay and prolongation of hatching, as well as death of embryos/chicks, and also a change of plumage pigmentation. Only two chicks of a total of 10 inoculated SPF eggs survived and were observed for 2 months. A gradual elimination of the CAstV genome was noted in this period. Moreover, a few contact-naive SPF chicks, which had been placed in the same cage, were infected with CAstV. Molecular characterization of detected CAstV was performed by nucleotide sequencing of the full ORF2 region encoding the capsid precursor protein gene. Phylogenetic studies showed that the PL/G059/2014 isolate clustered in the subgroup Aiii of CAstV. In the light of the new classification rules, the Polish PL/G059/2014 CAstV isolate could be assigned to a new species of the Avastrovirus genus.     

Stability, Controllability, and Observability of the “Four State” Model for the Sarcomeric Control of Contraction

A model of the sarcomeric control of contraction at various loading conditions has to maintain three cardinal features: stability, controllability (where the output can be controlled by the input), and observability (where the output reflects the effects of all the state variables). The suggested model of the sarcomere couples calcium kinetics with cross-bridge (XB) cycling and comprises two feedback mechanisms: (i) the cooperativity, whereby the number of force-generating (strong) XBs determines calcium affinity, regulates XB recruitment, and (ii) the mechanical feedback, whereby shortening velocity determines XBs cycling rate, controls the XBs contractile efficiency. The sarcomere is described by a set of four first-order nonlinear differential equations, utilizing the Matlab's Simulink software. Small oscillatory input was imposed when the state variables trajectories reached a steady state. The linearized state-space representations of the model were calculated for various initial sarcomere lengths. The analysis of the state-space representation validates the controllability and observability of the model. The model has four poles: three at the left side of the complex plane and one integrating pole at the origin. Therefore, the system is marginally stable. The Laplace transform confirms that the state representation is minimal and is therefore observable and controllable. The extension of the model to a multi-sarcomere lattice was explored, and the effects of inhomogeneity and nonuniform activation were described.     

Genomic and biological characterization of the Vibrio alginolyticus-infecting “Podoviridae” bacteriophage,vB_ValP_IME271

Virus Genes - As an opportunist pathogen, Vibrio alginolyticus (V. alginolyticus), causes disease in marine animals. Bacterial contamination of seafood is not uncommon, and phage therapy is...