Phylogeny and sequence variability of the Sarcocystis singaporensis Zaman and Colley, (1975) 1976 ssrDNA

The coccidium Sarcocystis singaporensis (Apicomplexa: Sarcocystidae) is a cyst-forming parasite with potential as a biological agent for the control of wild populations of rodents in non-native environments. Phylogenetic analysis based on the ssrDNA supports S. singaporensisisolates as a sister species to sarcosporidians transmitted between snakes and rodents but an association with the carnivore-ruminant Sarcocystis spp. could not be rejected by likelihood ratio tests. Four complete and six partial ssrDNA sequences representing this species are monophyletic in any tree reconstruction method; however, they possess very high pairwise distances of up to 0.053. The obtained sequences suggest the probable existence of at least two divergent paralogous ssrDNAs. Moreover, our results support the co-evolution of lsrDNA and ssrDNA in S. singaporensis. The utility of coccidian lsrDNA and ssrDNA for evolutionary studies and their abundance in the primary nucleotide databases is discussed.     

Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution

Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin γ-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.     

Energy landscape analysis of native folding of the prion protein yields the diffusion constant, transition path time, and rates

Protein folding is described conceptually in terms of diffusion over a configurational free-energy landscape, typically reduced to a one-dimensional profile along a reaction coordinate. In principle, kinetic properties can be predicted directly from the landscape profile using Kramers theory for diffusive barrier crossing, including the folding rates and the transition time for crossing the barrier. Landscape theory has been widely applied to interpret the time scales for protein conformational dynamics, but protein folding rates and transition times have not been calculated directly from experimentally measured free-energy profiles. We characterized the energy landscape for native folding of the prion protein using force spectroscopy, measuring the change in extension of a single protein molecule at high resolution as it unfolded/refolded under tension. Key parameters describing the landscape profile were first recovered from the distributions of unfolding and refolding forces, allowing the diffusion constant for barrier crossing and the transition path time across the barrier to be calculated. The full landscape profile was then reconstructed from force-extension curves, revealing a double-well potential with an extended, partially unfolded transition state. The barrier height and position were consistent with the previous results. Finally, Kramers theory was used to predict the folding rates from the landscape profile, recovering the values observed experimentally both under tension and at zero force in ensemble experiments. These results demonstrate how advances in single-molecule theory and experiment are harnessing the power of landscape formalisms to describe quantitatively the mechanics of folding.     

Comparison of Testing Methods for Evaluating the Resistance of Alkali-Activated Blast Furnace Slag Systems to Sulfur Dioxide

Alkali-activated systems (AAS) represent an ecologically and economically sustainable inorganic binder as an alternative to ordinary Portland cement (OPC). One of the main benefits of AAS is their durability in aggressive environments, which can be equal or even better than that of OPC. In this paper, the influence of the type of alkaline activator in alkali-activated blast furnace slag (AAS) in terms of resistance to sulfur dioxide corrosion was investigated. The durability testing process was based on the CSN EN ISO 3231 standard and simultaneously compared with mortar samples prepared by using Blastfurnace cement CEM III/A 32.5R. The degradation progress was evaluated by employing several different methods such as observing the compressive strength development, weight change evaluation, non-destructive testing methods like ultrasound or impact echo technique, or visual phenolphthalein technique. Subsequently, fundamental characterization of samples by the XRD method was performed during the degradation test. The obtained results indicate that none of the testing methods used could be prioritized over others to determine the resistance of AAS against the action of sulfur dioxide. For this reason, the durability testing of AAS remains an issue, and the development of specific standards considering the behavior of AAS seems necessary.     

A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.     

Clinical determinants of primary and secondary fatigue in patients with Parkinson’s disease

Clinical and psychosocial factors associated separately with primary and secondary fatigue in Parkinson’s disease (PD) patients have not been thoroughly studied before. The aim of our study was to assess factors associated with different fatigue domains in groups with primary and secondary fatigue in PD separately. We divided 165 non-demented PD patients according to the absence/presence of depression, anxiety and excessive somnolence into groups with primary fatigue (N = 63) and with secondary fatigue (N = 102). Fatigue domains examined using the multidimensional fatigue inventory were associated through multiple linear regression analyses for each group separately with sociodemographic data, disease duration, functional status as assessed by the Unified Parkinson’s Disease Rating Scale, treatment, depression, anxiety, excessive somnolence and sleep quality. Out of the assessed non-motor symptoms, fatigue was the most frequent (77.6 %). The prevalence of fatigue in the secondary fatigue group was significantly higher than in the primary fatigue group. Both fatigue groups differed significantly in factors associated with different fatigue domains. Functional status or other disease-related factors were not associated with primary fatigue. In the secondary fatigue group, we found associations between some fatigue domains and functional status, older age, male gender and higher anxiety scores. To our knowledge, this is the first study to separately describe clinical determinants and psychosocial factors associated with different fatigue domains in primary and secondary fatigue in PD, underlining the importance of distinguishing primary and secondary fatigue in future PD studies and clinical practice.     

The impact of sleep and mood disorders on quality of life in Parkinson’s disease patients

Sleep disturbances are common and often severe in patients with Parkinson’s disease (PD) and their symptoms can be present at any time of day. The purpose of our study was to examine how excessive daytime sleepiness or poor nocturnal sleep quality and mood disorders influence the quality of life (QoL) in PD patients. Ninety-three PD patients from eastern Slovakia were recruited (49.5% males, mean age 68.0 ± 9.5 years, mean disease duration 6.1 ± 5.9 years). Sleep disturbances were measured using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI); QoL with the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39); depression and anxiety with the Hospital Anxiety and Depression Scale (HADS) and disease severity with the Unified Parkinson’s Disease Rating Scale (UPDRS). χ ² test, bivariate correlations and multiple linear regressions were performed. PSQI and ESS had significant correlations with worse QoL (p < 0.01, p < 0.05, respectively). HADS-D (p < 0.01), HADS-A (p < 0.01), UPDRS (p < 0.01) and disease duration (p < 0.05) were also significantly related to worse QoL. In the linear regression analysis, however, only PSQI (p < 0.01), anxiety (p < 0.001) and UPDRS (p < 0.001) remained significant. The model with PSQI explained 74% of the variance, and the model with ESS explained 63% of the variance in PDQ-39 when analyses were performed separately. In an overall model, however, only PSQI remained significant, accounting for 82% of the variance in PDQ-39. Nighttime poor sleep and anxiety are important contributors leading to a worse QoL. As these are treatable conditions, they should be recognized by clinicians and managed properly.     

Treatment of Interictal Depression with Citalopram in Patients with Epilepsy

The purpose of this study is to assess the efficacy and safety of the selective serotonin-reuptake inhibitor (SSRI) citalopram in depressed epileptic patients. We evaluated 43 epileptic patients who suffered from depression and whose total score on the 21 items of the Hamilton Scale for Depression (HAMD 21) exceeded 15 points. These patients were examined by the psychiatrist and scaled before treatment and after 4 and 8 weeks of treatment with citalopram. The dose of citalopram was flexible, related to the actual condition of the patient. In each patient and in the whole group of patients we compared the monthly seizure frequency (total, partial seizures, generalized tonic–clonic seizures) recorded during treatment with citalopram with that recorded during the 2 months preceding the start of citalopram. During treatment we observed a decrease in the total score on the HAMD 21 from a mean initial value of 21.5 ± 2.9 (range, 17–26) prior to therapy 14.5 ± 2.9 (range, 10–19) (P < 0.001) after 4 weeks of treatment and to 9.9 ± 3.1 (range, 4–19) (P < 0.001) after 8 weeks of treatment. There were 9 (20.9%) responders after 4 weeks of treatment and 28 responders (65.1%) after 8 weeks, all of them with decrease on the HAMD 21 greater than 50%. Nausea was the most common adverse event in 7 patients (16.3%) during the first month of treatment and in 3 patients (6.9%) during the second month of treatment. Sexual dysfunction (decrease of libido) was reported in 2 (4.7%) male patients during the entire course of treatment. No seizure worsening was observed in our patients. Monthly seizure frequency did not change significantly: 2.24 (±0.76) seizures before treatment with citalopram, 2.29 (±0.81) seizures in the first month of treatment, 2.21 (±1.00) seizures in the second month of treatment. No occurrence of de novo generalized tonic–clonic seizures was recorded in individual patients. Citalopram is a safe and effective antidepressant in the treatment of depressed epileptic patients.     

Microhabitat distribution of <Emphasis Type="Italic">Pseudodactylogyrus anguillae</Emphasis> and <Emphasis Type="Italic">Pseudodactylogyrus bini</Emphasis> among and within gill arches of the European eel (<Emphasis Type="Italic">Anguilla anguilla</Emphasis> L.)

The outlying mean index (OMI) method was used to test for seasonal microhabitat partitioning in Pseudodactylogyrus anguillae and Pseudodactylogyrus bini communities parasitising European eel ( Anguilla anguilla L.) in four seasons. No differences in the occurrence of parasites were found in different seasons or on different gill arches. The OMI analysis showed that hemibranch separation and gill segments were the main factors explaining the variation in parasite niche occupation for the first factorial axis, which was generally more significant than the second factorial axis. The OMI and tolerance indices were compared for both species in the seasons studied, and the main differences between species indices were recorded. P. anguillae and P. bini communities were partitioned in the seasons with high epidemiological parameters of the infection. In the seasons with low epidemiological parameters, or in seasons when the parasite species preferred gill arches, the characters of gill division (lower level of gill division than gill arches) were not important for the partitioning of the Pseudodactylogyrus communities.