Effects of subchronic phencyclidine on behaviour of female rats on the elevated plus maze and open field

YesFemale hooded-Lister rats received either sub-chronic phencyclidine (PCP) (2 mg/kg, n=20) or vehicle (1 ml/kg, n=20) i.p. twice daily for seven days, followed by a seven-day washout period. Rats were challenged with acute PCP or vehicle and tested for locomotor activity to ensure hyperactivity was observed in the sub-chronic PCP treated rats. Rats were then tested on the elevated plus maze and in an open field for 10 minutes. Sub-chronic PCP did not significantly affect behaviour on the elevated plus maze or in the open field. In conclusion, sub-chronic PCP does not induce anxiety-like behaviour

Isolation rearing impairs novel object recognition and attentional set shifting performance in female rats

YesIt has been suggested that the isolation rearing paradigm models certain aspects of schizophrenia symptomatology. This study aimed to investigate whether isolation rearing impairs rats’ performance in two models of cognition: the novel object recognition (NOR) and attentional set-shifting tasks, tests of episodic memory and executive function, respectively. Two cohorts of female Hooded-Lister rats were used in these experiments. Animals were housed in social isolation or in groups of five from weaning, post-natal day 28. The first cohort was tested in the NOR test with inter-trial intervals (ITIs) of 1 min up to 6 h. The second cohort was trained and tested in the attentional set-shifting task. In the NOR test, isolates were only able to discriminate between the novel and familiar objects up to 1-h ITI, whereas socially reared animals remembered the familiar object up to a 4-h ITI. In the attentional set-shifting task, isolates were significantly and selectively impaired in the extra-dimensional shift phase of the task (P < 0.01). Rats reared in isolation show impaired episodic memory in the NOR task and reduced ability to shift attention between stimulus dimensions in the attentional set-shifting task. Because schizophrenic patients show similar deficits in performance in these cognitive domains, these data further support isolation rearing as a putative preclinical model of the cognitive deficits associated with schizophrenia

Dynein structure and power stroke

Dynein ATPases are microtubule motors that are critical to diverse processes such as vesicle transport and the beating of sperm tails; however, their mechanism of force generation is unknown. Each dynein comprises a head, from which a stalk and a stem emerge. Here we use electron microscopy and image processing to reveal new structural details of dynein c, an isoform from Chlamydomonas reinhardtii flagella, at the start and end of its power stroke. Both stem and stalk are flexible, and the stem connects to the head by means of a linker approximately 10 nm long that we propose lies across the head. With both ADP and vanadate bound, the stem and stalk emerge from the head 10 nm apart. However, without nucleotide they emerge much closer together owing to a change in linker orientation, and the coiled-coil stalk becomes stiffer. The net result is a shortening of the molecule coupled to an approximately 15-nm displacement of the tip of the stalk. These changes indicate a mechanism for the dynein power stroke

A Generalized Linear Model for Estimating Spectrotemporal Receptive Fields from Responses to Natural Sounds

In the auditory system, the stimulus-response properties of single neurons are often described in terms of the spectrotemporal receptive field (STRF), a linear kernel relating the spectrogram of the sound stimulus to the instantaneous firing rate of the neuron. Several algorithms have been used to estimate STRFs from responses to natural stimuli; these algorithms differ in their functional models, cost functions, and regularization methods. Here, we characterize the stimulus-response function of auditory neurons using a generalized linear model (GLM). In this model, each cell's input is described by: 1) a stimulus filter (STRF); and 2) a post-spike filter, which captures dependencies on the neuron's spiking history. The output of the model is given by a series of spike trains rather than instantaneous firing rate, allowing the prediction of spike train responses to novel stimuli. We fit the model by maximum penalized likelihood to the spiking activity of zebra finch auditory midbrain neurons in response to conspecific vocalizations (songs) and modulation limited (ml) noise. We compare this model to normalized reverse correlation (NRC), the traditional method for STRF estimation, in terms of predictive power and the basic tuning properties of the estimated STRFs. We find that a GLM with a sparse prior predicts novel responses to both stimulus classes significantly better than NRC. Importantly, we find that STRFs from the two models derived from the same responses can differ substantially and that GLM STRFs are more consistent between stimulus classes than NRC STRFs. These results suggest that a GLM with a sparse prior provides a more accurate characterization of spectrotemporal tuning than does the NRC method when responses to complex sounds are studied in these neurons

Sharp Alfvenic impulses in the near-Sun solar wind

Measurements of the near-Sun solar wind by Parker Solar Probe have revealed the presence of largenumbers of discrete Alfv ́enic impulses with an anti-Sunward sense of propagation. These are similarto those previously observed near 1 AU, in high speed streams over the Sun’s poles and at 60 solarradii. At 35 solar radii, however, they are typically shorter and sharper than seen elsewhere. Inaddition, these spikes occur in “patches” and there are also clear periods within the same stream whenthey do not occur; the timescale of these patches might be related to the rate at which the spacecraftmagnetic footpoint tracks across the coronal hole from which the plasma originated. While the velocityfluctuations associated with these spikes are typically under 100 km/s, due to the rather low Alfv ́enspeeds in the streams observed by the spacecraft to date, these are still associated with large angulardeflections of the magnetic field - and these deflections are not isotropic. These deflections do notappear to be related to the recently reported large scale, pro-rotation solar wind flow. Estimates ofthe size and shape of the spikes reveal high aspect ratio flow-aligned structures with a transverse scaleof≈104km. These events might be signatures of near-Sun impulsive reconnection events

Prevalence of Chlamydia trachomatis infection among women in a Middle Eastern community

BACKGROUND: Common vaginal infections that manifest in women are usually easily diagnosed. However, Chlamydia infection is often asymptomatic, leading to infertility before it is detected. If it occurs in pregnancy, it could lead to significant neonatal morbidity. It may also play a role with other viral infections for e.g. Human Papilloma Virus in the development of cervical cancer. The objective of this study was to determine the prevalence of Chlamydia infection in women undergoing screening for cervical abnormalities as a part of a research project in primary and secondary care institutions in the United Arab Emirates. METHODS: In this cross sectional study married women attending primary and secondary care participating in a large nationwide cervical abnormalities screening survey were offered Chlamydia testing using a commercially available test kit. This kit uses a rapid immunoassay for the direct detection of Chlamydia trachomatis antigen in endocervical swab specimens. As this study was performed in a traditional Islamic country, unmarried women were excluded from testing, as the management of any positive cases would create legal and social problems. All married women consenting to take part in the study were included irrespective of age. RESULTS: Of 1039 women approached over a period of eight months 919 (88.5%) agreed to participate. The number of women in the 16 to 19 years was small (0.01%) and 30% were aged over 40 years. The prevalence of Chlamydia infection in this study was 2.6% (95% confidence interval 1.2–3.3%), which was marginally higher in women screened in secondary care (p = 0.05). CONCLUSION: This is one of the few reports on the prevalence of Chlamydia infection in women from the Middle East. Due to cultural and social constraints this study excluded a large proportion of women aged less than 19 years of age. Hence no direct comparisons on prevalence could be made with studies from the West, which all included younger women at high risk of Chlamydia. However this study emphasizes the importance of cultural factors while interpreting results of studies from different cultures and communities

Bandit strategies in social search: the case of the DARPA red balloon challenge

Collective search for people and information has tremendously benefited from emerging communication technologies that leverage the wisdom of the crowds, and has been increasingly influential in solving time-critical tasks such as the DARPA Network Challenge (DNC, also known as the Red Balloon Challenge). However, while collective search often invests significant resources in encouraging the crowd to contribute new information, the effort invested in verifying this information is comparable, yet often neglected in crowdsourcing models. This paper studies how the exploration-verification trade-off displayed by the teams modulated their success in the DNC, as teams had limited human resources that they had to divide between recruitment (exploration) and verification (exploitation). Our analysis suggests that team performance in the DNC can be modelled as a modified multi-armed bandit (MAB) problem, where information arrives to the team originating from sources of different levels of veracity that need to be assessed in real time. We use these insights to build a data-driven agent-based model, based on the DNC’s data, to simulate team performance. The simulation results match the observed teams’ behavior and demonstrate how to achieve the best balance between exploration and exploitation for general time-critical collective search tasks.</p

Measuring the Quality of Observational Study Data in an International HIV Research Network

Observational studies of health conditions and outcomes often combine clinical care data from many sites without explicitly assessing the accuracy and completeness of these data. In order to improve the quality of data in an international multi-site observational cohort of HIV-infected patients, the authors conducted on-site, Good Clinical Practice-based audits of the clinical care datasets submitted by participating HIV clinics. Discrepancies between data submitted for research and data in the clinical records were categorized using the audit codes published by the European Organization for the Research and Treatment of Cancer. Five of seven sites had error rates >10% in key study variables, notably laboratory data, weight measurements, and antiretroviral medications. All sites had significant discrepancies in medication start and stop dates. Clinical care data, particularly antiretroviral regimens and associated dates, are prone to substantial error. Verifying data against source documents through audits will improve the quality of databases and research and can be a technique for retraining staff responsible for clinical data collection. The authors recommend that all participants in observational cohorts use data audits to assess and improve the quality of data and to guide future data collection and abstraction efforts at the point of care

Subdivisions of the Auditory Midbrain (N. Mesencephalicus Lateralis, pars dorsalis) in Zebra Finches Using Calcium-Binding Protein Immunocytochemistry

The midbrain nucleus mesencephalicus lateralis pars dorsalis (MLd) is thought to be the avian homologue of the central nucleus of the mammalian inferior colliculus. As such, it is a major relay in the ascending auditory pathway of all birds and in songbirds mediates the auditory feedback necessary for the learning and maintenance of song. To clarify the organization of MLd, we applied three calcium binding protein antibodies to tissue sections from the brains of adult male and female zebra finches. The staining patterns resulting from the application of parvalbumin, calbindin and calretinin antibodies differed from each other and in different parts of the nucleus. Parvalbumin-like immunoreactivity was distributed throughout the whole nucleus, as defined by the totality of the terminations of brainstem auditory afferents; in other words parvalbumin-like immunoreactivity defines the boundaries of MLd. Staining patterns of parvalbumin, calbindin and calretinin defined two regions of MLd: inner (MLd.I) and outer (MLd.O). MLd.O largely surrounds MLd.I and is distinct from the surrounding intercollicular nucleus. Unlike the case in some non-songbirds, however, the two MLd regions do not correspond to the terminal zones of the projections of the brainstem auditory nuclei angularis and laminaris, which have been found to overlap substantially throughout the nucleus in zebra finches

MIDA boronates are hydrolysed fast and slow by two different mechanisms

MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for small-molecule construction based on building blocks, largely because of the dramatic and general rate differences with which they are hydrolysed under various basic conditions. Yet the mechanistic underpinnings of these rate differences have remained unclear, which has hindered efforts to address the current limitations of this chemistry. Here we show that there are two distinct mechanisms for this hydrolysis: one is base mediated and the other neutral. The former can proceed more than three orders of magnitude faster than the latter, and involves a rate-limiting attack by a hydroxide at a MIDA carbonyl carbon. The alternative 'neutral' hydrolysis does not require an exogenous acid or base and involves rate-limiting B-N bond cleavage by a small water cluster, (H2O)n. The two mechanisms can operate in parallel, and their relative rates are readily quantified by (18)O incorporation. Whether hydrolysis is 'fast' or 'slow' is dictated by the pH, the water activity and the mass-transfer rates between phases. These findings stand to enable, in a rational way, an even more effective and widespread utilization of MIDA boronates in synthesis