What can we learn from inactivation studies? Lessons from auditory cortex

Wide variation in the outcome of auditory cortex inactivation has been an impediment to clear conclusions regarding the roles of the auditory cortex in behaviour. Inactivation methods differ in their efficacy and specificity. The likelihood of observing a behavioural deficit is additionally influenced by factors such as the species being used, task design and reward. A synthesis of previous results suggests that auditory cortex involvement is critical for tasks that require integrating across multiple stimulus features, and less likely to be critical for simple feature discriminations. New methods of neural silencing provide opportunities for spatially and temporally precise manipulation of activity, allowing perturbation of individual subfields and specific circuits

Electrically driven single electron spin resonance in a slanting Zeeman field

The rapidly rising fields of spintronics and quantum information science have led to a strong interest in developing the ability to coherently manipulate electron spins. Electron spin resonance (ESR) is a powerful technique to manipulate spins that is commonly achieved by applying an oscillating magnetic field. However, the technique has proven very challenging when addressing individual spins. In contrast, by mixing the spin and charge degrees of freedom in a controlled way through engineered non-uniform magnetic fields, electron spin can be manipulated electrically without the need of high-frequency magnetic fields. Here we realize electrically-driven addressable spin rotations on two individual electrons by integrating a micron-size ferromagnet to a double quantum dot device. We find that the electrical control and spin selectivity is enabled by the micro-magnet's stray magnetic field which can be tailored to multi-dots architecture. Our results demonstrate the feasibility of manipulating electron spins electrically in a scalable way.Comment: 25 pages, 6 figure

Effectiveness of Biosecurity Measures in Preventing Badger Visits to Farm Buildings

This is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Bovine tuberculosis caused by Mycobacterium bovis is a serious and economically important disease of cattle. Badgers have been implicated in the transmission and maintenance of the disease in the UK since the 1970s. Recent studies have provided substantial evidence of widespread and frequent visits by badgers to farm buildings during which there is the potential for close direct contact with cattle and contamination of cattle feed. METHODOLOGY: Here we evaluated the effectiveness of simple exclusion measures in improving farm biosecurity and preventing badger visits to farm buildings. In the first phase of the study, 32 farms were surveyed using motion-triggered infrared cameras on potential entrances to farm buildings to determine the background level of badger visits experienced by each farm. In the second phase, they were divided into four treatment groups; "Control", "Feed Storage", "Cattle Housing" and "Both", whereby no exclusion measures were installed, exclusion measures were installed on feed storage areas only, cattle housing only or both feed storage and cattle housing, respectively. Badger exclusion measures included sheet metal gates, adjustable metal panels for gates, sheet metal fencing, feed bins and electric fencing. Cameras were deployed for at least 365 nights in each phase on each farm. RESULTS: Badger visits to farm buildings occurred on 19 of the 32 farms in phase one. In phase two, the simple exclusion measures were 100% effective in preventing badger entry into farm buildings, as long as they were appropriately deployed. Furthermore, the installation of exclusion measures also reduced the level of badger visits to the rest of the farmyard. The findings of the present study clearly demonstrate how relatively simple practical measures can substantially reduce the likelihood of badger visits to buildings and reduce some of the potential for contact and disease transmission between badgers and cattle.This work was funded by Defra project number SE3119, http://www.defra.gov.uk/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Maternal Plasma 25-Hydroxyvitamin D Concentrations and the Risk for Gestational Diabetes Mellitus

Background: Evidence is accumulating for a role of vitamin D in maintaining normal glucose homeostasis. However, studies that prospectively examined circulating concentrations of 25-hydroxyvitamin D (25-[OH] D) in relation to diabetes risk are limited. Our objective is to determine the association between maternal plasma 25-[OH] D concentrations in early pregnancy and the risk for gestational diabetes mellitus (GDM). Methods: A nested case-control study was conducted among a prospective cohort of 953 pregnant women. Among them, 57 incident GDM cases were ascertained and 114 women who were not diagnosed with GDM were selected as controls. Controls were frequency matched to cases for the estimated season of conception of the index pregnancy. Results: Among women who developed GDM, maternal plasma 25-[OH] D concentrations at an average of 16 weeks of gestation were significantly lower than controls (24.2 vs. 30.1 ng/ml, P<0.001). This difference remained significant (3.62 ng/ml lower on average in GDM cases than controls (P value = 0.018)) after the adjustment for maternal age, race, family history of diabetes, and pre-pregnancy BMI. Approximately 33% of GDM cases, compared with 14% of controls (P<0.001), had maternal plasma 25-[OH] D concentrations consistent with a pre-specified diagnosis of vitamin D deficiency (<20 ng/ml). After adjustment for the aforementioned covariates including BMI, vitamin D deficiency was associated with a 2.66-fold (OR (95% CI): 2.66 (1.01–7.02)) increased GDM risk. Moreover, each 5 ng/ml decrease in 25-[OH] D concentrations was related to a 1.29-fold increase in GDM risk (OR (95% CI): 1.29 (1.05–1.60)). Additional adjustment for season and physical activity did not change findings substantially. Conclusions: Findings from the present study suggest that maternal vitamin D deficiency in early pregnancy is significantly associated with an elevated risk for GDM

Effectiveness of esterified whey proteins fractions against Egyptian Lethal Avian Influenza A (H5N1)

<p>Abstract</p> <p>Background</p> <p>Avian influenza A (H5N1) virus is one of the most important public health concerns worldwide. The antiviral activity of native and esterified whey proteins fractions (α- lactalbumin, β- lactoglobulin, and lactoferrin) was evaluated against A/chicken/Egypt/086Q-NLQP/2008 HPAI (H5N1) strain of clade 2.2.1 (for multiplicity of infection (1 MOI) after 72 h of incubation at 37°C in the presence of 5% CO₂) using MDCK cell lines.</p> <p>Result</p> <p>Both the native and esterified lactoferrin seem to be the most active antiviral protein among the tested samples, followed by β- lactoglobulin. α-Lactalbumin had less antiviral activity even after esterification.</p> <p>Conclusion</p> <p>Esterification of whey proteins fractions especially lactoferrin and β-lactoglobulin enhanced their antiviral activity against H5N1 in a concentration dependent manner.</p

A novel underuse model shows that inactivity but not ovariectomy determines the deteriorated material properties and geometry of cortical bone in the tibia of adult rats

Our goal in this study was to determine to what extent the physiologic consequences of ovariectomy (OVX) in bones are exacerbated by a lack of daily activity such as walking. We forced 14-week-old female rats to be inactive for 15 weeks with a unique experimental system that prevents standing and walking while allowing other movements. Tibiae, femora, and 4th lumbar vertebrae were analyzed by peripheral quantitative computed tomography (pQCT), microfocused X-ray computed tomography (micro-CT), histology, histomorphometry, Raman spectroscopy, and the three-point bending test. Contrary to our expectation, the exacerbation was very much limited to the cancellous bone parameters. Parameters of femur and tibia cortical bone were affected by the forced inactivity but not by OVX: (1) cross-sectional moment of inertia was significantly smaller in Sham-Inactive rat bones than that of their walking counterparts; (2) the number of sclerostin-positive osteocytes per unit cross-sectional area was larger in Sham-Inactive rat bones than in Sham-Walking rat bones; and (3) material properties such as ultimate stress of inactive rat tibia was lower than that of their walking counterparts. Of note, the additive effect of inactivity and OVX was seen only in a few parameters, such as the cancellous bone mineral density of the lumbar vertebrae and the structural parameters of cancellous bone in the lumbar vertebrae/tibiae. It is concluded that the lack of daily activity is detrimental to the strength and quality of cortical bone in the femur and tibia of rats, while lack of estrogen is not. Our inactive rat model, with the older rats, will aid the study of postmenopausal osteoporosis, the etiology of which may be both hormonal and mechanical

Structure and function of mammalian cilia

In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation. This view has had unanticipated consequences for our understanding of developmental processes and human disease

Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells

<p>Abstract</p> <p>Background</p> <p>Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines.</p> <p>Methods</p> <p>Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis.</p> <p>Results</p> <p>We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis.</p> <p>Conclusions</p> <p>The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first evidence that altered primary cilium expression and function may be part of some malignant phenotypes. Further, we provide the first evidence that ciliogenesis is not an all or none process; rather defects can arrest this process at various points, particularly at the stage subsequent to basal body association with the plasma membrane.</p

How Abnormal Is the Behaviour of Captive, Zoo-Living Chimpanzees?

Background. Many captive chimpanzees (Pan troglodytes) show a variety of serious behavioural abnormalities, some of which have been considered as possible signs of compromised mental health. The provision of environmental enrichments aimed at reducing the performance of abnormal behaviours is increasing the norm, with the housing of individuals in (semi-)natural social groups thought to be the most successful of these. Only a few quantitative studies of abnormal behaviour have been conducted, however, particularly for the captive population held in zoological collections. Consequently, a clear picture of the level of abnormal behaviour in zoo-living chimpanzees is lacking. Methods. We present preliminary findings from a detailed observational study of the behaviour of 40 socially-housed zoo-living chimpanzees from six collections in the United States of America and the United Kingdom. We determined the prevalence, diversity, frequency, and duration of abnormal behaviour from 1200 hours of continuous behavioural data collected by focal animal sampling. Results, conclusion, and significance. Our overall finding was that abnormal behaviour was present in all sampled individuals across six independent groups of zoo-living chimpanzees, despite the differences between these groups in size, composition, housing, etc. We found substantial variation between individuals in the frequency and duration of abnormal behaviour, but all individuals engaged in at least some abnormal behaviour and variation across individuals could not be explained by sex, age, rearing history or background (defined as prior housing conditions). Our data support a conclusion that, while most behaviour of zoo-living chimpanzees is ‘normal’ in that it is typical of their wild counterparts, abnormal behaviour is endemic in this population despite enrichment efforts. We suggest there is an urgent need to understand how the chimpanzee mind copes with captivity, an issue with both scientific and welfare implications