Use of micro-computed tomography imaging and porosity measurements as indicators of collagen preservation in archaeological bone

Collagen isolated from archaeological bone is a common material for radiocarbon dating, stable isotope analysis, and zooarchaeology by mass spectrometry (ZooMS). However, not all bones contain extant collagen, leading to unnecessary destruction of unproductive bones and wasted laboratory time and resources. An aim of this research is to study bone diagenesis, particularly collagen destruction, in an effort to develop a minimally destructive method for identifying bones with high collagen content. In a multi-method study of variably preserved bones from Etton, Cambridgeshire, UK, we examined material properties of Neolithic cattle and sheep bones including porosity, surface area, and elemental composition. Micro-computed tomography (microCT) is an imaging technique that furnishes three-dimensional images of mineralized materials such as bone. Cortical bone porosity, the percentage of total bone volume consisting of empty space as calculated using microCT, can act as a proxy for bone collagen preservation. In general, bones with high cortical porosity are unlikely to contain sufficient collagen for further analysis. Bones with apparently low cortical porosity have a more varied range of collagen preservation. Bone samples with low porosity and no extant collagen often contain micropores with a diameter of 10 nm or less that cannot be seen in microCT images but are apparent in pore size distributions measured by mercury porosimetry, and indicated by high surface areas measured by nitrogen adsorption. Furthermore, a re-evaluation of light-induced breakdown spectroscopy data from this same assemblage confirms that ratios of calcium to fluorine may likewise indicate the state of diagenesis

Experimental modulation of capsule size in Cryptococcus neoformans

Experimental modulation of capsule size is an important technique for the study of the virulence of the encapsulated pathogen Cryptococcus neoformans. In this paper, we summarize the techniques available for experimental modulation of capsule size in this yeast and describe improved methods to induce capsule size changes. The response of the yeast to the various stimuli is highly dependent on the cryptococcal strain. A high CO(2) atmosphere and a low iron concentration have been used classically to increase capsule size. Unfortunately, these stimuli are not reliable for inducing capsular enlargement in all strains. Recently we have identified new and simpler conditions for inducing capsule enlargement that consistently elicited this effect. Specifically, we noted that mammalian serum or diluted Sabouraud broth in MOPS buffer pH 7.3 efficiently induced capsule growth. Media that slowed the growth rate of the yeast correlated with an increase in capsule size. Finally, we summarize the most commonly used media that induce capsule growth in C. neoformans

IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen

Reward and Punishment Sensitivity in Children with ADHD: Validating the Sensitivity to Punishment and Sensitivity to Reward Questionnaire for Children (SPSRQ-C)

This study validates the Sensitivity to Punishment and Sensitivity to Reward Questionnaire for children (SPSRQ-C), using a Dutch sample of 1234 children between 6–13 years old. Factor analysis determined that a 4-factor and a 5-factor solution were best fitting, explaining 41% and 50% of the variance respectively. The 4-factor model was highly similar to the original SPSRQ factors found in adults (Punishment Sensitivity, Reward Responsivity, Impulsivity/Fun-Seeking, and Drive). The 5-factor model was similar to the 4-factor model, with the exception of a subdivision of the Punishment Sensitivity factor into a factor with ‘social-fear’ items and a factor with ‘anxiety’ items. To determine external validity, scores of three groups of children with attention deficit hyperactivity disorder (ADHD) were compared on the EFA models: ADHD-only (n = 34), ADHD and autism spectrum disorder (ADHD+ASD; n = 22), ADHD and oppositional defiant disorder (ADHD+ODD; n = 22). All ADHD groups scored higher than typical controls on Reward Responsivity and on the ‘anxiety’ factor (n = 75). The ADHD-only and ADHD+ODD group scored higher than other groups on Impulsivity/Fun-Seeking and Drive, while the ADHD+ASD group scored higher on Punishment Sensitivity. The findings emphasize the value of the SPSRQ-C to quickly and reliably assess a child’s sensitivity to reinforcement, with the aim to provide individually-tailored behavioral interventions that utilize reward and reprimands

Long-term results of diaphragmatic plication in adults with unilateral diaphragm paralysis

<p>Abstract</p> <p>Background</p> <p>In this study we aimed to evaluate the long-term outcome of diaphragmatic plication for symptomatic unilateral diaphragm paralysis.</p> <p>Methods</p> <p>Thirteen patients who underwent unilateral diaphragmatic plication (2 patients had right, 11 left plication) between January 2003 and December 2006 were evaluated. One patient died postoperatively due to sepsis. The remaining 12 patients [9 males, 3 females; mean age 60 (36-66) years] were reevaluated with chest radiography, flouroscopy or ultrasonography, pulmonary function tests, computed tomography (CT) or magnetic resonance imaging (MRI), and the MRC/ATS dyspnea score at an average of 5.4 (4-7) years after diaphragmatic plication.</p> <p>Results</p> <p>The etiology of paralysis was trauma (9 patients), cardiac by pass surgery (3 patients), and idiopathic (1 patient). The principle symptom was progressive dyspnea with a mean duration of 32.9 (22-60) months before surgery. All patients had an elevated hemidiaphragm and paradoxical movement radiologically prior to surgery. There were partial atelectasis and reccurent infection of the lower lobe in the affected side on CT in 9 patients. Atelectasis was completely improved in 9 patients after plication. Preoperative spirometry showed a clear restrictive pattern. Mean preoperative FVC was 56.7 ± 11.6% and FEV1 65.3 ± 8.7%. FVC and FEV1 improved by 43.6 ± 30.6% (p < 0.001) and 27.3 ± 10.9% (p < 0.001) at late follow-up. MRC/ATS dyspnea scores improved 3 points in 11 patients and 1 point in 1 patient at long-term (p < 0.0001). Eight patients had returned to work at 3 months after surgery.</p> <p>Conclusions</p> <p>Diaphragmatic plication for unilateral diaphragm paralysis decreases lung compression, ensures remission of symptoms, and improves quality of life in long-term period.</p

Low Pathogenic Avian Influenza Isolates from Wild Birds Replicate and Transmit via Contact in Ferrets without Prior Adaptation

Direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. Currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. We have previously demonstrated the capacity of numerous North American avian influenza viruses isolated from wild birds to infect and induce lesions in the respiratory tract of mice. In this study, two isolates from shorebirds that were previously examined in mice (H1N9 and H6N1 subtypes) are further examined through experimental inoculations in the ferret with analysis of viral shedding, histopathology, and antigen localization via immunohistochemistry to elucidate pathogenicity and transmission of these viruses. Using sequence analysis and glycan binding analysis, we show that these avian viruses have the typical avian influenza binding pattern, with affinity for cell glycoproteins/glycolipids having terminal sialic acid (SA) residues with α 2,3 linkage [Neu5Ac(α2,3)Gal]. Despite the lack of α2,6 linked SA binding, these AIVs productively infected both the upper and lower respiratory tract of ferrets, resulting in nasal viral shedding and pulmonary lesions with minimal morbidity. Moreover, we show that one of the viruses is able to transmit to ferrets via direct contact, despite its binding affinity for α 2,3 linked SA residues. These results demonstrate that avian influenza viruses, which are endemic in aquatic birds, can potentially infect humans and other mammals without adaptation. Finally this work highlights the need for additional study of the wild bird subset of influenza viruses in regard to surveillance, transmission, and potential for reassortment, as they have zoonotic potential

Can Motivation Normalize Working Memory and Task Persistence in Children with Attention-Deficit/Hyperactivity Disorder? The Effects of Money and Computer-Gaming

Visual-spatial Working Memory (WM) is the most impaired executive function in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Some suggest that deficits in executive functioning are caused by motivational deficits. However, there are no studies that investigate the effects of motivation on the visual-spatial WM of children with- and without ADHD. Studies examining this in executive functions other than WM, show inconsistent results. These inconsistencies may be related to differences in the reinforcement used. The effects of different reinforcers on WM performance were investigated in 30 children with ADHD and 31 non-ADHD controls. A visual-spatial WM task was administered in four reinforcement conditions: Feedback-only, 1 euro, 10 euros, and a computer-game version of the task. In the Feedback-only condition, children with ADHD performed worse on the WM measure than controls. Although incentives significantly improved the WM performance of children with ADHD, even the strongest incentives (10 euros and Gaming) were unable to normalize their performance. Feedback-only provided sufficient reinforcement for controls to reach optimal performance, while children with ADHD required extra reinforcement. Only children with ADHD showed a decrease in performance over time. Importantly, the strongest incentives (10 euros and Gaming) normalized persistence of performance in these children, whereas 1 euro had no such effect. Both executive and motivational deficits give rise to visual-spatial WM deficits in ADHD. Problems with task-persistence in ADHD result from motivational deficits. In ADHD-reinforcement studies and clinical practice (e.g., assessment), reinforcement intensity can be a confounding factor and should be taken into account. Gaming can be a cost-effective way to maximize performance in ADHD

Cyclin D1 and D3 expression in melanocytic skin lesions

Cyclins, cyclin-dependent kinases, as well as proteins cooperating with them are responsible for cell cycle regulation which is crucial for normal development, injury repair, and tumorigenesis. D-type cyclins regulate G1 cell cycle progression by enhancing the activities of cyclin-dependent kinases, and their expression is frequently altered in tumors. Disturbances in cyclin expression were also reported in melanocytic skin lesions. The objective of the study was to evaluate the expression of cyclins D1 and D3 in common, dysplastic, and malignant melanocytic skin lesions. Forty-eight melanocytic skin lesions including common nevi (10), dysplastic nevi (24), and melanomas (14) were diagnosed by dermoscopy and excised. Expression of cyclin D1 and D3 was detected by immunohistochemistry and quantified as percentage of immunostained cell nuclei in each sample. In normal skin, expression of cyclins D1 and D3 was not detected. The mean percentage of cyclin D1-positive nuclei was 7.75% for melanoma samples, 5% for dysplastic nevi samples, and 0.34% for common nevi samples. For cyclin D3, the respective values were 17.8, 6.4, and 1.8%. Statistically significant differences in cyclin D1 expression were observed between melanomas and common nevi as well as between dysplastic and common nevi (p = 0.0001), but not between melanomas and dysplastic nevi. Cyclin D3 expression revealed significant differences between all investigated lesion types (p = 0.0000). The mean cyclin D1 and D3 scores of melanomas with Breslow thickness <1 mm and >1 mm were not significantly different. G1/S abnormalities are crucial for the progression of malignant melanoma, and enhanced cyclin D1 and D3 expression leading to increased melanocyte proliferation is observed in both melanoma and dysplastic nevi. In histopathologically ambiguous cases, lower cyclin D3 expression in dysplastic nevi can be a diagnostic marker for that lesion type

Partial Depletion of Natural CD4+CD25+ Regulatory T Cells with Anti-CD25 Antibody Does Not Alter the Course of Acute Influenza A Virus Infection

Foxp3+ CD4+ regulatory T cells represent a T cell subset with well-characterized immunosuppressive effects during immune homeostasis and chronic infections, and there is emerging evidence to suggest these cells temper pulmonary inflammation in response to acute viral infection. Recent studies have demonstrated treatment with PC61 CD25-depleting antibody potentiates inflammation in a murine model of RSV infection, while paradoxically delaying recruitment of CD8+ T cells to the site of inflammation. The present study therefore sought to examine the role of these cells in a murine model of acute influenza A virus infection through the administration of PC61 CD25-depleting antibody. PC61 antibody is able to partially deplete CD25+Foxp3+ regulatory T cells to a comparable degree as seen within previous work examining RSV, however this does not alter influenza A-virus induced mortality, weight loss, viral clearance and cellularity within the lung. Collectively, these data demonstrate that partial depletion of CD4+CD25+ regulatory T cells with PC61 antibody does not alter the course of influenza A virus infection

High sensitivity (1)H-NMR spectroscopy of homeopathic remedies made in water

BACKGROUND: The efficacy of homeopathy is controversial. Homeopathic remedies are made via iterated shaking and dilution, in ethanol or in water, from a starting substance. Remedies of potency 12 C or higher are ultra-dilute (UD), i.e. contain zero molecules of the starting material. Various hypotheses have been advanced to explain how a UD remedy might be different from unprepared solvent. One such hypothesis posits that a remedy contains stable clusters, i.e. localized regions where one or more hydrogen bonds remain fixed on a long time scale. High sensitivity proton nuclear magnetic resonance spectroscopy has not previously been used to look for evidence of differences between UD remedies and controls. METHODS: Homeopathic remedies made in water were studied via high sensitivity proton nuclear magnetic resonance spectroscopy. A total of 57 remedy samples representing six starting materials and spanning a variety of potencies from 6 C to 10 M were tested along with 46 controls. RESULTS: By presaturating on the water peak, signals could be reliably detected that represented H-containing species at concentrations as low as 5 μM. There were 35 positions where a discrete signal was seen in one or more of the 103 spectra, which should theoretically have been absent from the spectrum of pure water. Of these 35, fifteen were identified as machine-generated artifacts, eight were identified as trace levels of organic contaminants, and twelve were unexplained. Of the unexplained signals, six were seen in just one spectrum each. None of the artifacts or unexplained signals occurred more frequently in remedies than in controls, using a p < .05 cutoff. Some commercially prepared samples were found to contain traces of one or more of these small organic molecules: ethanol, acetate, formate, methanol, and acetone. CONCLUSION: No discrete signals suggesting a difference between remedies and controls were seen, via high sensitivity (1)H-NMR spectroscopy. The results failed to support a hypothesis that remedies made in water contain long-lived non-dynamic alterations of the H-bonding pattern of the solvent