Plasma chemistry and urine analysis in Salmonella-induced polyuria in racing pigeons (Columba livia)

Polyuria-polydipsia is a frequent observation in pigeons with salmonellosis. These are accompanied by a decreased albumin/globulin ratio, increased creatinine and haptoglobin concentrations, and decrease in the chloride concentration in the blood plasma. The urine was found to have a low density with red and white blood cells frequently present in the sediment. A water deprivation test was conducted on three animals: polyuria disappeared and plasma urea increased significantly.     

The incidence of error in young children's Wh-questions.

Many current generativist theorists suggest that young children possess the grammatical principles of inversion required for question formation but make errors because they find it difficult to learn language-specific rules about how inversion applies. The present study analyzed longitudinal spontaneous sampled data from twelve 2-3-year-old English speaking children and the intensive diary data of 1 child (age 2;7 [years;months] to 2;11) in order to test some of these theories. The results indicated significantly different rates of error use across different auxiliaries. In particular, error rates differed across 2 forms of the same auxiliary subtype (e.g., auxiliary is vs. are), and auxiliary DO and modal auxiliaries attracted significantly higher rates of errors of inversion than other auxiliaries. The authors concluded that current generativist theories might have problems explaining the patterning of errors seen in children's questions, which might be more consistent with a constructivist account of development. However, constructivists need to devise more precise predictions in order to fully explain the acquisition of questions.     

The topical organization of the afferents to the caudatoputamen of the rat. A horseradish peroxidase study

The aim of the present study was to assess (1) whether the various brain areas known to send projections to the neostriatum of the rat (neocortex, thalamus, substantia nigra, ventral tegmental area and dorsal raphe nucleus) project to all parts of this structure, and (2) whether the subcortical projections show a topical organization. For these purposes, small deposits of horseradish peroxidase were delivered by iontophoretic application, so that the whole extent of the caudatoputamen could be covered in a total of 40 rats.Labeled cortical cells were present mainly in lamina V, and showed a roughly topographical organization. Small numbers of labelled cells were observed in the basal nucleus of the amygdala after injections into the dorsal and central parts of the caudatoputamen. The cells of origin of thalamic afferents to the neostriatum were found not only in the intralaminar nuclei, but also in various other anterior, ‘midline’, and posterior nuclei (e.g. the medial part of the medial geniculate body). In the thalamostriatal projection a topical organization was demonstrated, consisting of oblique thalamic zones, which cross the borders of several thalamic nuclei and project to different parts of the neostriatum. In the substantia nigra and ventral tegmental area many retrogradely labelled cells were present. This nigrostriatal projection appears to be organized along an oblique longitudinal neostriatal axis. The nucleus raphes dorsalis was labelled most abundantly after caudal and ventrolateral injections into the caudatoputamen.It is concluded that, despite the homogeneous cytoarchitectonic structure of the caudatoputamen in the rat, this brain area is rather heterogeneous as regards its afferent connections. In fact each part of the neostriatum receives a specific and unique combination of afferents. The main changes in the input of the neostriatum appear to occur along an oblique longitudinal axis, from the most rostromedial and dorsal part to the caudolateral and ventral part. Such a topographical organization suggests that the neostriatum is likely to be involved in very complex integrative functions involving several brain areas.     

Organization of secondary lymphoid tissue and local IgE formation to Staphylococcus aureus enterotoxins in nasal polyp tissue

BACKGROUND: Bilateral nasal polyposis (NP) is characterized by high concentrations of IgE in NP tissue, which show no relation to the atopic status. We aimed to study the relationship between systemic and local IgE formation, nasal carriage of Staphylococcus aureus and nasal polyposis. METHODS: In serum and nasal tissue homogenates from 24 NP patients and 12 controls, we determined concentrations of total IgE and IgE antibodies to inhalant allergens and S. aureus enterotoxins (SAEs; A,B,C,D,E,TSST) by ImmunoCAP. Tissue cryosections were stained for CD3, CD20, CD38, CD23, FcepsilonRI, IgE and SEA/SEB. RESULTS: We demonstrated a higher incidence of S. aureus colonization (17/24) and IgE antibodies to SAEs in NP tissue (12/24) compared with controls (3/12 and 0/12, respectively). Total IgE and IgE antibodies in serum and NP tissue were dissociated because of local polyclonal IgE formation in NP tissue. Staining of NP tissue revealed follicular structures characterized by B and T cells, and lymphoid accumulations with diffuse plasma cell infiltration. CONCLUSIONS: We demonstrated the organization of secondary lymphoid tissue in polyp tissue and a polyclonal hyper-immunoglobulinemia E associated with the presence of IgE antibodies to SAEs, colonization with S. aureus, and tissue eosinophilia in a relevant subgroup of polyp patients.     

Macrophage mannose receptor in chronic sinus disease

BACKGROUND: The role of infectious agents in the onset and maintenance of chronic sinus disease is still not fully understood. Macrophage mannose receptor (MMR), an innate pattern recognizing receptor, capable of phagocytosis of invaders and signal transduction for proinflammatory mechanisms, might be of importance in immune interactions in chronic sinus disease. OBJECTIVE: We examined the MMR in sinonasal airway mucosa to evaluate its possible role in chronic rhinosinusitis (CS) and nasal polyposis (NPs). METHODS: Surgical samples from patients with sinonasal disease were investigated with real-time RT-PCR for quantification of MMR mRNA expression, and the presence and location of MMR-positive cells was analysed by immunohistochemistry. RESULTS: Quantification of MMR mRNA showed a statistically significant higher expression in NPs compared to CS without NP and controls. Immunohistochemistry revealed expression of MMR in all tissue samples; however, in NP we found an enhanced positive cellular staining including cell aggregates. CONCLUSIONS: We could demonstrate for the first time that the expression of MMR is significantly upregulated in NP compared to patients with CS without NP or turbinate tissue of controls. Macrophages expressing MMR, accumulated in cell aggregates in NPs, play a possible key role in pathogen-macrophage interaction in NP disease.     

Influence of the punch diameter and curvature on the yield pressure of MCC-compacts during Heckel analysis.

The volume reduction behaviour of powders has been quantified by means of the 'in-die' yield pressure (YP) using Heckel analysis. However, because different YPs are reported for the same material, the experimental conditions influencing this material-constant were investigated. Silicified microcrystalline cellulose was compressed into flat-faced and convex tablets using a compaction simulator instrumented with load and displacement transducers. During compression, upper and lower punch force and displacement data were recorded and corrected for punch deformation. A symmetrical triangle wave compression profile was used and the instantaneous punch velocity was kept constant (5mm/s). Individual tablet height and weight were used for Heckel analysis. The influence of the 'effective compression pressure' (P(EFF)) (ranging from 10 to 350 MPa), punch diameter (PD) (4, 9.5 and 12 mm) and filling depth (FD) (4.5, 7.5 and 10.5mm) on YP was statistically evaluated using Response Surface Modelling software. A quadratic surface response equation, describing the relationship between P(EFF), PD, FD and YP, was proposed for concave (Adj R(2): 0.8424; S.D.: 14.60 MPa) and flat-faced (Adj R(2): 0.8409; S.D.: 4.49 MPa) punches. YP and tensile strength were mainly determined by P(EFF), irrespective of punch curvature. FD and PD had only a minor influence on the YP, although more pronounced for the concave punches. The method used resulted in reproducible P(EFF) and tensile strength values and the flat-faced tablets showed less weight variation. Flat-faced punches are preferred over punches with a concave surface when investigating the volume reduction behaviour of a powder by means of Heckel analysis and the experimental parameters should be reported.     

A ribavirin-induced ORF2 single-nucleotide variant produces defective hepatitis E virus particles with immune decoy function

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically transmitted viral hepatitis worldwide. Ribavirin (RBV) is currently the only treatment option for many patients; however, cases of treatment failures or posttreatment relapses have been frequently reported. RBV therapy was shown to be associated with an increase in HEV genome heterogeneity and the emergence of distinct HEV variants. In this study, we analyzed the impact of eight patient-derived open reading frame 2 (ORF2) single-nucleotide variants (SNVs), which occurred under RBV treatment, on the replication cycle and pathogenesis of HEV. The parental HEV strain and seven ORF2 variants showed comparable levels of RNA replication in human hepatoma cells and primary human hepatocytes. However, a P79S ORF2 variant demonstrated reduced RNA copy numbers released in the supernatant and an impairment in the production of infectious particles. Biophysical and biochemical characterization revealed that this SNV caused defective, smaller HEV particles with a loss of infectiousness. Furthermore, the P79S variant displayed an altered subcellular distribution of the ORF2 protein and was able to interfere with antibody-mediated neutralization of HEV in a competition assay. In conclusion, an SNV in the HEV ORF2 could be identified that resulted in altered virus particles that were noninfectious in vitro and in vivo, but could potentially serve as immune decoys. These findings provide insights in understanding the biology of circulating HEV variants and may guide development of personalized antiviral strategies in the future.

Despite its rising global prevalence, hepatitis E is a disease that is mostly overlooked. Every year, more than 44,000 people die as a result of ∼20 million infections worldwide (1). Healthy individuals usually display no or only mild symptoms of viral hepatitis, such as fever, nausea, vomiting, and abdominal pain (2), while patients with preexisting liver disease, pregnant women, and immunocompromised individuals suffer from liver cirrhosis and liver failure (3). Pregnant women additionally present with increased mortality rates of >25% (4). Despite those liver-associated problems, there are also extrahepatic manifestations, such as hematopoietic disease, neurological disorders, and renal injury (5–9). The underlying agent, hepatitis E virus (HEV), is classed within the species of Paslahevepirus balayani (10), formerly known as Orthohepevirus A, which includes isolates from human, swine, wild boar, rat, and other mammals. HEV is a quasienveloped virus existing as both enveloped and non-enveloped particles (11, 12). To date, eight distinct genotypes (GT) of this species of the single-stranded RNA virus have been described (13), which display similar genomic structures. The positive orientated HEV genome is organized in three main open reading frames (ORF1 to ORF3) with a total length of 7.2 kb. Nonstructural proteins forming the HEV replicase complex, such as the RNA-dependent RNA polymerase (RdRp), RNA helicase, or methyltransferase, are encoded by ORF1, while the viral capsid protein is encoded by ORF2. During the HEV replication cycle, HEV produces at least three forms of ORF2 protein: infectious ORF2 (ORF2i), glycosylated ORF2 (ORF2g), and cleaved ORF2 (ORF2c) protein (14). The ORF2i protein is the structural component of infectious particles that is likely derived from the assembly of the intracellular ORF2 (ORF2intra) protein form. In contrast, ORF2g and ORF2c protein are not associated with infectious virions, but secreted in large amounts and are the most abundant antigens detected in patient sera (14). ORF3 encodes for a functional ion channel required for assembly and release of infectious particles by interacting with a variety of host factors (15).In immunocompetent patients, acute hepatitis E usually does not involve antiviral therapy; however, chronically infected and immunocompromised patients often require clinical intervention to clear the infection. Antiviral therapies include pegylated interferon (16–18), successfully implemented for many virus infections, and sofosbuvir (19, 20), a direct acting antiviral against hepatitis C virus, both of which have not yet been systematically evaluated in the context of HEV therapy. Recent studies have investigated the antiviral potential of silvestrol (21), zinc salts (22), and other possible drug candidates in vitro [reviewed in detail by Kinast et al. (23)], but the findings remain to be clinically validated. Lacking specific treatment options, the broad antiviral ribavirin (RBV) (24) is frequently used off-label. However, RBV therapy is often discontinued due to adverse side effects and is only effective in ∼80% of patients, implying that 20% of treated patients remain viremic (25). RBV treatment is specifically contraindicated in pregnant women and can give rise to variants such as G1634R, as well as other amino acid substitutions within the ORF1-encoded polyprotein, potentially contributing to treatment failure and poor clinical long-term outcomes (26–28). In this context, we recently identified viral populations of HEV harboring variations in the capsid-encoding ORF2 region during RBV therapy. With the use of an efficient HEV cell-culture model system, we characterized the impact of these ORF2 variants in the HEV replication cycle.     

The Use of Cyclopenta[2,1‐b;3,4‐b′]dithiophene Analogues for the Development of Low‐Bandgap Materials

This paper presents the synthesis and characterization of low‐bandgap materials based on cyclopenta[1,2‐b;3,4‐b′]dithiophene (CPDT). An array of electron‐poor monomers is synthesized and used to prepare homo‐ and alternating donor–acceptor copolymers. This yields polymers with low bandgaps (E_g = 1.12–1.23 eV) and broad light absorption (400–1100 nm). The influence of the electron‐withdrawing substituent and the donor material on the polymer properties is studied. It is demonstrated that the low bandgap is not a result of intramolecular charge transfer, but of a transition localized in the electron‐poor CPDT monomer. The bandgap can be correlated with the substituent on the CPDT monomer and is relatively independent of other parameters, resulting in materials with an easily tunable bandgap.