What kind of movement detector is triggering the landing response of the housefly?

As shown before, the latency of the housefly's landing response depends on the conditions of the visual stimulus (Borst 1986). Accordingly, the latency can be used to characterize the movement detection system which is triggering the landing response.The stimulus was a sinusoidal periodic pattern of vertical stripes presented bilaterally in the frontolateral eye region of the fly. It started to move, simultaneously on either side, from front to back at a given time. The latency of the response was measured by means of an infrared light-beam that was interrupted whenever the fly lifted its forelegs to assume a preprogrammed landing posture (Fig. 1). The latency was found to vary in a range from 60 ms up to several seconds depending on the pattern's spatial wavelength , contrast frequency cf and contrast C.For sufficiently high pattern contrast the optimum of the reaction (minimum latency) is found at spatial wavelengths of 30–40° and contrast frequencies of 8–17 periods/s (Fig. 3a). This is about 2–10 times more than is anticipated from the optomotor response under similar conditions. Evaluation of the optimum contrast frequency cf _OPT at different wavelengths shows that cf _OPT is not independent of (Fig. 3b, solid line). The same is true for the contrast dependence of the reaction: reduction of the contrast leads not only to a general decrease in the response amplitudes (prolongation of the latency) (Fig. 4a), but also to a shift of cf _OPT towards lower contrast frequencies (Fig. 4b, solid line).In the theory of the correlation-type movement detector (Reichardt 1961) which underlies the optomotor response of flies the dependence of cf _OPT on pattern wavelength and/or pattern contrast is not expected under stationary conditions. However, as shown by computer simulation all experimental results can be explained by a homogeneous retinotopic array of correlation movement detectors (Fig. 2) if their response under non-stationary conditions is taken into account. We simply assume that the spatially and temporally integrated output of the movement detectors is evaluated by a threshold device (Fig.5). The correlation-type movement detection in combination with a temporal integrator system predicts the rather complex dependence of the optimum contrast frequency on pattern wavelength and pattern contrast (dashed lines in Fig. 3b and 4b) and provides the missing explanation of the variable latencies of the landing response.Comparing the parameters of the correlation-type movement detector derived in the present study with those of the optomotor response, the landing response seems to use the same type of movement detection system. To account for the high wavelength optimum, however, the input elements of the movement detection system of the landing response might have an increased visual field (e.g. by pooling neighbouring visual elements) and, accordingly, a reduced visual acuity as compared with the input elements of the optomotor system.Abbreviations (°) spatial pattern wavelength - w(°/s) angular velocity of the pattern - cf (Hz) contrast frequency=w/ - cf _OPT(Hz) cf leading to the shortest latency - (Hz) angular frequency=2cf - I mean luminance of the pattern - I modulation amplitude of the pattern - C pattern contrast=I/ - (ms) time constant of a filter - (°) angle between the optical axis of neighbouring visual elements - (°) acceptance angle of visual elements     

Application of MIRU–VNTR on smear slides: a shortcut for detection of polyclonal infections in tuberculosis patients

Mixed (polyclonal) infections are one of the main problems in tuberculosis (TB) management. The best available method for detecting polyclonal infections in TB is mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU–VNTR). According to multiple studies, MIRU–VNTR method can be applied to detect TB-related polyclonal infections in sputum samples or cultures. Setup of MIRU–VNTR on smear slides can be an efficient approach, regardless of the limitations of cultures and sputum samples in many laboratories. The present study aimed at investigating the diagnostic potential of MIRU–VNTR on smear slides in detecting mixed infections. Ziehl–Neelsen-stained microscopic slides were prepared from 14 clinical specimens. For amplifying 24 MIRU–VNTR loci, PCR assay was performed on the smear slides, clinical specimens, and cultures. Based on the 24-locus MIRU–VNTR analysis, polyclonal infections were reported in 42.85% of smear slides, while the corresponding rate was estimated at 57.1% (8/14) in the clinical samples. In the corresponding cultures, the rate of mixed infection was 7.14% (1/14). Use of smear slides can be a safe option for transferring clinical specimens between environmental and reference laboratories. Considering their significant impact on TB treatment, it is essential to diagnose mixed infections in low-resource countries with a high prevalence of mixed infections. The present findings show that direct MIRU–VNTR on smear slides can be conveniently used for the detection of mixed infections.

     

Effect of PLCβ4 in the thalamus on the EEG in REM sleep

Sleep and Biological Rhythms -     

Complexity of resting-state EEG activity in the patients with early-stage Parkinson’s disease

To investigate the abnormal brain activities in the early stage of Parkinson’s disease (PD), the electroencephalogram (EEG) signals were recorded with 20 channels from non-dementia PD patients (18 patients, 8 females) and age matched healthy controls (18 subjects, 8 females) during the resting state. Two methods based on the ordinal patterns of the recorded series, i.e., permutation entropy (PE) and order index (OI), were introduced to characterize the complexity of the cortical activities for two groups. It was observed that the resting-state EEG of PD patients showed lower PE and higher OI than healthy controls, which indicated that the early-stage PD caused the reduced complexity of EEG. We further applied two methods to determine the complexity of EEG rhythms in five sub-bands. The results showed that the gamma, beta and alpha rhythms of PD patients were characterized by lower PE and higher OI, i.e., reduced complexity, than healthy subjects. No significant differences were observed in theta or delta rhythms between two groups. The findings suggested that PE and OI were promising methods to detect the abnormal changes in the dynamics of EEG signals associated with early-stage PD. Further, such changes in EEG complexity may be the early markers of the cortical or subcortical dysfunction caused by PD.     

Stimulatory effect of PGF2α on PRL based on experimental inhibition of each hormone in mares

During the luteolytic period in mares, the peak of 65% of pulses of a PGF2α metabolite (PGFM) and the peak of a pulse of PRL have been reported to occur at the same hour. It is unknown whether the synchrony reflects an effect of PGF2α on PRL or vice versa. Controls, a flunixin meglumine (FM)-treated group (to inhibit PGF2α), and a bromocriptine-treated group (to inhibit PRL), were used at 14 days postovulation in June and in September (n = 6 mares/group/mo). Blood samples were collected hourly from just before treatment (Hour 0) to Hour 10. Concentrations of PGFM in the FM group were lower (P < 0.05) at Hours 4 to 6 than in the controls in each month, but bromocriptine had no detected effects on PGFM. Concentrations of PGFM averaged over all groups and within each group did not differ between June and September. Compared to the controls, concentrations of PRL in June were lower (P < 0.05) in the FM group at Hours 4 to 8 and in the bromocriptine group at Hours 4 to 10. Concentration of PRL averaged over groups was lower (P < 0.0001) in September (0.9 ± 0.05 ng/mL, mean ± SEM) than in June (3.0 ± 0.3 ng/mL). Results supported the hypothesis that the positive association between PGFM and PRL concentrations in mares represents an effect of PGF2α on PRL rather than an effect of PRL on PGF2α.     

Effects of r—HuEPO on the biophysical characteristics of erythrocyte membrane in patients with anemia of chronic renal failure

Using electron spin resonance (ESR) spin labeling technique,we have studied the conformation of sulfhydryl groups(-SH) binding sites in membrane proteins and mem brane fluidity of red blood cells(RBCs) from two groups of patients with anemia of chronic renal failure(ACRF).One of the groups is composed of patients who were untreated with recombinant human erythropoietin(r-HuEPO),and the other is composed of patients who were treated with r-HuEPO.The results indicated:1)the conformation of SH group binding site in RBC membrane proteins from former group was different from those of healty people.2)the fluidity in the region near the surface of RBC membrane from former group was lower than those of healthy people.3)However,the above biophysical properties of RBC membrane from later group were normal.We concluded that RBC membrane in patients with ACRF was abnormal,and the treatment of r-HuEPO may promote the production of normal RBCs,thus ameliorate the biophysical properties of RBCs from the patients with ACRF.     

Metabolomic study of the bone trabecula of osteonecrosis femoral head patients based on UPLC–MS/MS

The severity and/or progression of osteonecrosis of the femoral head (ONFH) are commonly assessed by radiography, nuclear magnetic resonance image which aren’t invariably correlated to severity of disease and may be disturbed by other factors. Consequently, exploring the novel biochemical signatures of ONFH may be beneficial for diagnosing and understanding this disease. In this work, a bone trabecula metabolomics was undertaken to determine the expression pattern of low molecular mass metabolites in patients of femoral head necrosis based on the ultra-performance liquid chromatography/time-of-flight tandem mass spectrometry (UPLC/TOF MS/MS). Histological study showed that necrotic bone was characterized by necrosis, fibrosis and lacuna, but adjacent “normal” bone was pathologically normal. Principal component analysis in combination with orthogonal partial least-squares discrimination analysis was used to find out changed metabolites. MS/MS was used to speculate the corresponding molecule. Both osteonecrotic bone trabecula (ONBT) and adjacent “normal” bone trabecula (ANBT) showed higher levels of amino acids, such as proline, arginine, glutamine, dipeptides and lower levels of antioxidants. Most disrupted lipids, such as fatty acid esters, glycerophospholipids, sphingolipids, were found in osteonecrotic zone. The area under the receiver operating characteristic curve of combinational biomarkers (d-arginine, l-proline, l-carnitine, inosine) in ONBT and ANBT was 0.996 and 0.950, respectively. Our findings might provide a significant insight to understand the metabolic mechanism and diagnosis biomarkers of ONFH in the future.     

Reproducible Analysis of Post-Translational Modifications in Proteomes—Application to Human Mutations

Background

Protein post-translational modifications (PTMs) are an important aspect of protein regulation. The number of PTMs discovered within the human proteome, and other proteomes, has been rapidly expanding in recent years. As a consequence of the rate in which new PTMs are identified, analysis done in one year may result in different conclusions when repeated in subsequent years. Among the various functional questions pertaining to PTMs, one important relationship to address is the interplay between modifications and mutations. Specifically, because the linear sequence surrounding a modification site often determines molecular recognition, it is hypothesized that mutations near sites of PTMs may be more likely to result in a detrimental effect on protein function, resulting in the development of disease.

Methods and Results

We wrote an application programming interface (API) to make analysis of ProteomeScout, a comprehensive database of PTMs and protein information, easy and reproducible. We used this API to analyze the relationship between PTMs and human mutations associated with disease (based on the ‘Clinical Significance’ annotation from dbSNP). Proteins containing pathogenic mutations demonstrated a significant study bias which was controlled for by analyzing only well-studied proteins, based on their having at least one pathogenic mutation. We found that pathogenic mutations are significantly more likely to lie within eight amino acids of a phosphoserine, phosphotyrosine or ubiquitination site when compared to mutations in general, based on a Fisher’s Exact test. Despite the skew of pathogenic mutations occurring on positively charged arginines, we could not account for this relationship based only on residue type. Finally, we hypothesize a potential mechanism for a pathogenic mutation on RAF1, based on its proximity to a phosphorylation site, which represents a subtle regulation difference that may explain why its biochemical effect has failed to be uncovered previously. The combination of the API and a dynamically expanding PTM database will make the reanalysis of this question and other systems-level questions easier in the future.     

Application of IMRT in adjuvant treatment of soft tissue sarcomas of the thigh—Preliminary results

Background

Fracture of the femur is the most frequent late complication in patients with soft tissue sarcomas (STS) who receive external beam radiotherapy after limb-sparing surgery.

Aim

To reduce the risk of bone fracture following radiotherapy of STS of the thigh, we minimized the dose to the femur and to surrounding normal tissues by applying intensity modulated radiation therapy (IMRT). We report preliminary results of post-surgery IMRT of the thigh in patients with STS in this extremity.

Materials and methods

10 adult patients undergoing post-operative radiotherapy of STS of the thigh were treated using IMRT. Clinical IMRT plans with simultaneous integrated boost (SIB) and 3-phase three-dimensional conformal radiotherapy (3D-CRT) were designed to adequately treat the planning target volume and to spare the femur to the largest extent possible. Dose distributions and dose-volume histograms were compared.

Results

For either technique, a comparable target coverage was achieved; however, target volume was better covered and critical structures were better spared in IMRT plans. Mean and maximum doses to OAR structures were also significantly reduced in the IMRT plans. On average, the mean dose to the femur in 3D-CRT plans was about two times higher than that in IMRT plans.

Conclusion

Compared with 3D-CRT, the application of IMRT improves the dose distribution within the concave target volumes and reduces dose to the OAR structures without compromising target coverage.     

Changes in sleep characteristics of rat preclinical model of Parkinson’s disease based on attenuation of the ubiquitin—proteasome system activity in the brain

Numerous experimental and epidemiological data indicate a high significance of environmental neurotoxins, specifically, inhibitors of the ubiquitin–proteasome system, in pathogenesis of Parkinson’s disease (PD). To develop a preclinical model of PD in rats we used a technique of intranasal administration of lactacystin, a natural proteasome inhibitor, into the brain. It was found that three weeks after the first lactacystin administration it induced a little degeneration of dopaminergic neurons in the olfactory bulb and substantia nigra pars compacta without any olfactory dysfunction and motor behavior disorders. Besides, its effect led to the appearance of some signs of sleep disorders: increased somnolence (especially in the dark, active daily phase), fragmentation of slow-wave sleep, decreased EEG delta rhythm during slow-wave sleep. These signs share some similarity with PD and could be useful in clinical studies for the quick search for polysomnographic markers of the early PD stage.     

Comparing the midpoint and endpoint approaches based on ReCiPe—a study of commercial buildings in Hong Kong

Purpose

Life cycle assessment (LCA) has been increasingly implemented in analyzing the environmental performance of buildings and construction projects. To assess the life cycle environmental performance, decision-makers may adopt the two life cycle impact assessment (LCIA) approaches, namely the midpoint and endpoint models. Any imprudent usage of the two approaches may affect the assessment results and thus lead to misleading findings. ReCiPe, a well-known work, includes a package of LCIA methods to provide assessments on both midpoint and endpoint levels. This study compares different potential LCIA results using the midpoint and endpoint approaches of ReCiPe based on the assessment of a commercial building in Hong Kong.

Methods

This paper examines 23 materials accounting for over 99 % of the environmental impacts of all the materials consumed in commercial buildings in Hong Kong. The midpoint and endpoint results are compared at the normalization level. A commercial building in Hong Kong is further studied to provide insights as a real case study. The ranking of impact categories and the contributions from various construction materials are examined for the commercial building. Influence due to the weighting factors is discussed.

Results and discussion

Normalization results of individual impact categories of the midpoint and endpoint approaches are consistent for the selected construction materials. The difference in the two approaches can be detected when several impact categories are considered. The ranking of materials is slightly different under the two approaches. The ranking of impact categories demonstrates completely different features. In the case study of a commercial building in Hong Kong, the contributions from subprocesses are different at the midpoint and endpoint. The weighting factors can determine not only the contributions of the damage categories to the total environment, but also the value of a single score.

Conclusions

In this research, the midpoint and endpoint approaches are compared using ReCiPe. Information is whittled down from the inventories to a single score. Midpoint results are comprehensive while endpoint results are concise. The endpoint approach which provides additional information of damage should be used as a supplementary to the midpoint model. When endpoint results are asked for, a LCIA method like ReCiPe that provides both the midpoint and endpoint analysis is recommended. This study can assist LCA designers to interpret the midpoint and endpoint results, in particular, for the assessment of commercial buildings in Hong Kong.     

Role of PGF2α in luteolysis based on inhibition of PGF2α synthesis in the mare

The effects of inhibition of PGF2α synthesis on luteolysis in mares and on the incidence of prolonged luteal activity were studied in controls and in a group treated with flunixin meglumine (FM), a PGF2α inhibitor (n = 6/group). The FM was given every 8 hours (1.0 mg/kg) on each of Days 14.0 to 16.7. Concentration (pg/mL) of PGF2α metabolite averaged over 8 hours of hourly blood sampling at the beginning of each day, was lower in the FM group than in the controls on Day 14 after ovulation (6.7 ± 1.3 vs. 13.8 ± 2.9, P < 0.05), Day 15 (15.0 ± 3.9 vs. 35.2 ± 10.4, P < 0.10), and Day 16 (21.9 ± 5.7 vs. 54.7 ± 11.4, P < 0.03). Concentration (ng/mL) of progesterone (P4) was greater in the FM group than in the controls on Day 14 (10.1 ± 0.9 vs. 7.7 ± 0.9, P < 0.08), Day 15 (9.2 ± 1.0 vs. 4.3 ± 1.0, P < 0.008), and Day 16 (5.6 ± 1.6 vs. 1.2 ± 0.4, P < 0.02). The interval from ovulation to the beginning of a decrease in P4 and to the end of luteolysis (P4 < 1 ng/mL) was each delayed (P < 0.03) by ∼1 day in the FM group. Intervals involving the luteal phase were long (statistical outliers, P < 0.05) in two mares in the FM group, indicating prolonged luteal activity. Results supported the hypotheses that (1) inhibition of PGF2α synthesis interferes with luteolysis in mares and (2) inhibition of PGF2α at the expected time of luteolysis may lead to prolonged luteal activity.     

Application of cyclodextrinase in non-complexant production of γ-cyclodextrin

The production of γ-cyclodextrin usually includes the utilization of organic complexants. However, the non-complexant production of γ-cyclodextrin is always being explored due to the defects of organic complexants. However, in non-complexant production, the separation of γ-cyclodextrin from α- and β-cyclodextrin is still a challenge. Here, the selective hydrolysis ability of a cyclodextrinase designated PpCD (cyclodextrinase from Palaeococcus pacificus) on α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin was proved. The k_cat/K_m values of PpCD for α-cyclodextrin and β-cyclodextrin were roughly 12-fold and 5-fold higher than that of γ-cyclodextrin. It was proved that PpCD had selective hydrolysis ability and its γ-cyclodextrin purification performance was apparent on various simulated cyclodextrin mixtures with reported proportions derived from different CGTases. Besides, the hydrolysis temperature was optimized and it could be seen that 85°C was appropriate for the production of γ-cyclodextrin. In addition, the production of γ-cyclodextrin was achieved by using PpCD in the γ-CGTase reaction products.