Improvement of signal-to-noise ratio in electroantennogram responses using multiple insect antennae

Using an array of insect antennae connected in series or in parallel, electroantennogram (EAG) responses and noise levels were investigated in an attempt to improve signal-to-noise (S/N) ratio and sensitivity. Both the EAG response amplitude and noise level increased when the antennae of male Helicoverpa zea (Lepidoptera: Noctuidae) were connected in series. Due to lower relative increase in noise level than EAG amplitude as the number of antennae increased, the S/N ratio was also significantly improved by the serial connection. As a result the sensitivity of EAG was improved by the serial connection, which showed ca. ten-fold improvement in the threshold detection levels compared with a single antenna when four antennae were connected in series. In contrast to the serial connection, there were no differences in EAG amplitudes and overall noise levels when different numbers of antennae were connected in parallel. When only large-amplitude noise was taken into account, however, the S/N ratio was somewhat improved by the parallel connection. The frequency of overall noise remained at the same level both in the serial and in the parallel connection. However, the frequency of the large-amplitude noise increased in serial connection but decreased in parallel connection. The present study clearly indicates that both the sensitivity and S/N ratio of the EAG biosensor could be significantly improved by using the multiple antennal connections.     

A Missense Mutation in the SERPINH1 Gene in Dachshunds with Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene.     

Homozygosity for a Missense Mutation in SERPINH1, which Encodes the Collagen Chaperone Protein HSP47, Results in Severe Recessive Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is characterized by bone fragility and fractures that may be accompanied by bone deformity, dentinogenesis imperfecta, short stature, and shortened life span. About 90% of individuals with OI have dominant mutations in the type I collagen genes COL1A1 and COL1A2. Recessive forms of OI resulting from mutations in collagen-modifying enzymes and chaperones CRTAP, LEPRE1, PPIB, and FKBP10 have recently been identified. We have identified an autosomal-recessive missense mutation (c.233T>C, p.Leu78Pro) in SERPINH1, which encodes the collagen chaperone-like protein HSP47, that leads to a severe OI phenotype. The mutation results in degradation of the endoplasmic reticulum resident HSP47 via the proteasome. Type I procollagen accumulates in the Golgi of fibroblasts from the affected individual and a population of the secreted type I procollagen is protease sensitive. These findings suggest that HSP47 monitors the integrity of the triple helix of type I procollagen at the ER/cis-Golgi boundary and, when absent, the rate of transit from the ER to the Golgi is increased and helical structure is compromised. The normal 3-hydroxylation of the prolyl residue at position 986 of the triple helical domain of proα1(I) chains places the role of HSP47 downstream from the CRTAP/P3H1/CyPB complex that is involved in prolyl 3-hydroxylation. Identification of this mutation in SERPINH1 gives further insight into critical steps of the collagen biosynthetic pathway and the molecular pathogenesis of OI.     

Models of production lines with flexible workstations

This article presents models of production line systems with two flexible workstations. Flexible stations have the capability of switching from one operation to another when they become either blocked or starved. The objective is to determine and compare the production rates of serial and parallel arrangements of the workstations. It is shown that, in general, the serial arrangement achieves higher efficiency. Under some specific assumptions, however, both arrangements have the same production rate. An extension of the analysis of two stations to n stations for the parallel case is also presented.     

Identification of a novel COL1A1 frameshift mutation, c.700delG,in a Chinese osteogenesis imperfecta family

Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients’ diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI.     

A novel deletion mutation involving TMEM38B in a patient with autosomal recessive osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a hereditary bone disease characterized by decreased bone density and multiple fractures, usually inherited in an autosomal dominant manner. Several gene encoding proteins related to collagen metabolism have been described in some cases of autosomal recessive OI (including CRTAP, LEPRE1, PPIB, FKBP65, SERPINF1, BMP1, WNT1, FKBP10). Recently, TMEM38B, a gene that encodes TRIC-B, a monovalent cation-specific channel involved in calcium flux from intracellular stores and in cell differentiation, has been associated with autosomal recessive OI. Here, we describe the second deletion-mutation involving the TMEM38B gene in an 11 year-old Albanian female with a clinical phenotype of OI, born to parents with suspected consanguinity. SNP array analysis revealed a homozygous region larger than 2 Mb that overlapped with the TMEM38B locus and was characterized by a 35 kb homozygous deletion involving exons 1 and 2 of TMEM38B gene.     

Allomorphy and the question of abstractness: evidence from German

A model of grammar needs to reconcile the undesirability inherent to allomorphy, the apparent extra burden on learning and memory, with its occurrence and possible stability. OT approaches this task by positing an anti-allomorphy constraint, henceforth referred to as “OO-correspondence”, which requires leveling (i.e. sameness of sound structure) in related word forms (Benua 1997). The occurrence of allomorphy then indicates crucial domination of OO-correspondence by other constraints.To assess the adequacy of this proposal it is necessary to establish the level of abstractness at which OO-correspondence applies and to examine the consequences of this decision for ranking order. While proponents of OT tacitly assume the level in question to be rather concrete, the notion of allomorphy as originally envisioned in Structuralism was defined by distinctness at a more abstract level referred to as “phonemic” (Harris 1942; Nida 1944). The basic intuition here is that the defining property of subphonemic sound properties, their conditionedness by context, entails that whatever burden they put on learning and memory is of a fundamentally different nature than that entailed by phonemic distinctness. The evidence from German supports that intuition in that leveling can be shown to target phonemic sound structure to the exclusion of subphonemic properties. Allomorphy, defined by phonemic alternation, tends to serve phonological optimization in closed class items (function words, affixes) while serving to express morphological distinctions in open class items. The key to demonstrating the correlations in question lies in the discernment of phonemic structure, which is therefore at the core of the article.     

Weak radicals,weak suppletion,and phonological indices in Semitic

Paster (2014) has argued that grammar does not distinguish between weak and strong suppletion. This claim is countered in this paper, in an analysis of allomorphic effects in several Semitic languages. What has been traditionally called “root” is broken down into three levels: the formless index (Harley 2014), the phonological index (Borer 2005, 2009, 2013) and its underlying representation. The distinction between the first two leads to a principled structural difference between weak and strong suppletion. Several test cases are presented that require a distinction between the latter two. Two general conclusions are drawn: (1) allomorphy at the different levels has different functions, and (2) in the Semitic root-and-pattern system, weakly suppletive allomorphy never targets the root as a whole; there is no root allomorphy in Semitic.     

Towards a theory without adjacency: hyper-contextual VI-rules

It has been proposed that allomorphy and suppletion is restricted not only by (various conceptions of) cyclic locality, but also by adjacency of elements. Embick (2010) proposes that two elements can only enter into an relationship of allomorphy if they are linearly adjacent to each other, whereas Adger et al. (2003) and Bobaljik (2012) argue that elements must be structurally adjacent.In this paper, we show that there are both empirical and conceptual problems for adjacency based theories and we argue instead in favour of a cyclic locality only view; whereby allomorphic relations are not universally sensitive to adjacency restrictions. Apparent arguments in favour of adjacency are shown to be the result accessibility or of ‘hyper-contextual’ rules of vocabulary insertion, which make reference to multiple nodes, which combine together to serve as the context for suppletion.     

Osteogenesis imperfecta

Osteogenesis imperfecta (OI) is the most frequently occurring congenital disorder with an increased fracture rate and systemic skeletal involvement. The vast majority of patients have an autosomal dominant form of OI resulting from a mutation in one of the two type I collagen genes COL1A1 or COL1A2. Since 2006, eight genes for autosomal recessive forms of the disorder have been identified, as well as one additional gene for autosomal dominant OI. Our knowledge concerning molecular pathophysiology has been substantially broadened, such that the paradigm of OI as a pure ??collagenopathy?? no longer applies and the clinical classification system will have to be revised. Standard therapy for the more severe forms of OI comprises intravenous administration of bisphosphonates. Additional elements of a multimodal therapeutic concept include surgical intervention for bone deformities or fractures and physiotherapy.     

PPIB Mutations Cause Severe Osteogenesis Imperfecta

Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the α1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the α1 chains of collagen type I.     

New Hypothesis on Antigenic Competition based on Cell Interactions in the Immune Response

ATTEMPTS to elucidate the immunological deficit associated with antigenic competition¹ have produced two divergent theories: (1) a cellular exhaustion or depletion theory in which it is postulated that different, non-cross-reacting antigens compete with each other for a hypothetical immunocompetent, pleuripotent, lymphoid cell occurring in limited numbers^2,3 and (2) a humoral theory which postulates the release of soluble inhibitory factors as a consequence of immunization⁴, which could have immuno-regulatory significance. Such factors have not been isolated, Athough there is no direct evidence for the cellular exhaustion or depletion theory, some indirect evidence has been advanced³. It has been a difficult theory to accept, however, for it seems to violate the generally accepted tenets of clonal selection theories of immunity⁵.     

Genotype-Phenotype Relationship and Follow-up Analysis of a Chinese Cohort With Osteogenesis Imperfecta

ObjectiveTo evaluate the genotype-phenotype relationship and the effect of treatment on the clinical course of osteogenesis imperfecta (OI).MethodsWe established a Chinese hospitalized cohort with OI and followed them up for an average of 6 years. All patients were confirmed as having OI using whole-exome sequencing. We analyzed the genotype-phenotype relationship based on different types, pathogenic mechanisms, and gene inheritance patterns of OI. Additionally, we assessed whether there was a difference in treatment efficacy based on genotype.ResultsOne hundred sixteen mutations in 6 pathogenic genes (COL1A1, COL1A2, IFITM5, SERPINF1, FKBP10, and WNT1) were identified in 116 patients with type I, III, IV, V, VI, XI, or XV OI. Compared with patients with COL1A1 mutations, patients with COL1A2 mutations were younger at the time of the first fracture, whereas other phenotypes were similar. When 3 groups (helical, haploinsufficiency, and non-collagen I gene mutations) were compared, patients with helical mutations were the shortest and most prone to dentinogenesis imperfecta. Patients with haploinsufficiency mutations were the oldest at the time of the first fracture. Moreover, patients with non-collagen I gene mutations were least susceptible to blue sclerae and had the highest fracture frequency. Furthermore, there were some minor phenotypic differences among non-collagen I gene mutations. Interestingly, pamidronate achieved excellent results in the treatment of patients with OI, and the treatment effect appeared to be unrelated to their genotypes.ConclusionOur findings indicated a genotype-phenotype relationship and a similar effect of pamidronate treatment in patients with OI, which could provide a basis for guiding clinical treatment and predicting OI prognosis.     

SL2-like spliced leader RNAs in the basal nematode Prionchulus punctatus: New insight into the evolution of nematode SL2 RNAs

Spliced-leader (SL) trans-splicing has been found in all molecularly characterized nematode species to date, and it is likely to be a nematode synapomorphy. Most information regarding SL trans-splicing has come from the study of nematodes from a single monophyletic group, the Rhabditida, all of which employ SL RNAs that are identical to, or variants of, the SL1 RNA first characterized in Caenorhabditis elegans. In contrast, the more distantly related Trichinella spiralis, belonging to the subclass Dorylaimia, utilizes a distinct set of SL RNAs that display considerable sequence diversity. To investigate whether this is true of other members of the Dorylaimia, we have characterized SL RNAs from Prionchulus punctatus. Surprisingly, this revealed the presence of a set of SLs that show clear sequence similarity to the SL2 family of spliced leaders, which have previously only been found within the rhabditine group (which includes C. elegans). Expression of one of the P. punctatus SL RNAs in C. elegans reveals that it can compete specifically with the endogenous C. elegans SL2 spliced leaders, being spliced to the pre-mRNAs derived from downstream genes in operons, but does not compete with the SL1 spliced leaders. This discovery raises the possibility that SL2-like spliced leaders were present in the last common ancestor of the nematode phylum.     

A new Escherichia coli gene,fdrA, identified by suppression analysis of dominant negative FtsH mutations

An Escherichia coli membrane protein, FtsH, has been implicated in several cellular processes, including integration of membrane proteins, translocation of secreted proteins, and degradation of some unstable proteins. However, how it takes part in such diverse cellular events is largely unknown. We previously isolated dominant negative ftsH mutations and proposed that FtsH functions in association with some other cellular factor(s). To test this proposal we isolated multicopy suppressors of dominant negative ftsH mutations. One of the multicopy suppressor clones contained an N-terminally truncated version of a new gene that was designated fdrA. The FdrA fragment suppressed both of the phenotypes — increased abnormal translocation of a normally cytoplasmic domain of a model membrane protein and retardation of protein export — caused by dominant negative FtsH proteins. The intact fdrA gene (11.9 min on the chromosome) directed the synthesis of a 60 kDa protein in vitro.     

Component-dependent allomorphy and paradigm accessibility: evidence from Hebrew

This study examines allomorphy in vowel selection in Hebrew. We address the formation of adjectives and passive verbs in a specific morphological pattern with stem-medial glottals. While the normative vowel that precedes the glottal is o, there are cases where it is colloquially u. We provide empirical evidence for this variation (or lack thereof), arguing that vowel selection results from the distinction between adjectives and passive verbs and, more generally, from the component of the grammar where they are derived, the lexicon and the syntax. Studies of Hebrew have shown that a has a more morphological-lexical status, as it is typical of word formation processes, while e has a phonological status as it is the default vowel in epenthesis. A previous study has also shown that a is more typical of the lexicon and e is more typical of the syntax. We propose a similar distinction between o and u; u tends to be selected in passive formation in the syntax, while o is selected for words stored in the lexicon. In addition, we claim that the occurrence of each allomorph is triggered by uniformity to other forms in different paradigms that are taken into account in word formation. The study provides further evidence to a new type of allomorphy, whose evidence for conditioning is not purely phonological or morpho-syntactic, but rather depends on the locus of word formation. It highlights the strong correlation between form, meaning and the relevant grammatical component in word formation.     

Ovitrap surveillance of dengue vector mosquitoes in Bandung City,West Java Province,Indonesia

Larval surveillance is the central approach for monitoring dengue vector populations in Indonesia. However, traditional larval indices are ineffective for measuring mosquito population dynamics and predicting the dengue transmission risk. We conducted a 14-month ovitrap surveillance. Eggs and immature mosquitoes were collected on a weekly basis from an urban village of Bandung, namely Sekejati. Ovitrap-related indices, namely positive house index (PHI), ovitrap index (OI), and ovitrap density index (ODI), were generated and correlated with environmental variables, housing type (terraced or high-density housing), ovitrap placement location (indoor or outdoor; household or public place), and local dengue cases. Our results demonstrated that Aedes aegypti was significantly predominant compared with Aedes albopictus at each housing type and ovitrap placement location. Ovitrap placement locations and rainfall were the major factors contributing to variations in PHI, OI, and ODI, whereas the influences of housing type and temperature were subtle. Indoor site values were significantly positively correlated to outdoor sites’ values for both OI and ODI. OI and ODI values from households were best predicted with those from public places at 1- and 0-week lags, respectively. Weekly rainfall values at 4- and 3-week lags were the best predictors of OI and ODI for households and public places, respectively. Monthly mean PHI, OI, and ODI were significantly associated with local dengue cases. In conclusion, ovitrap may be an effective tool for monitoring the population dynamics of Aedes mosquitoes, predicting dengue outbreaks, and serving as an early indicator to initiate environmental clean-up. Ovitrap surveillance is easy for surveyors if they are tasked with a certain number of ovitraps at a designated area, unlike the existing larval surveillance methodology, which entails identifying potential breeding sites largely at the surveyors’ discretion. Ovitrap surveillance may reduce the influence of individual effort in larval surveillance that likely causes inconsistency in results.     

The Study of Object-Oriented Motor Imagery Based on EEG Suppression

Motor imagery is a conventional method for brain computer interface and motor learning. To avoid the great individual difference of the motor imagery ability, object-oriented motor imagery was applied, and the effects were studied. Kinesthetic motor imagery and visual observation were administered to 15 healthy volunteers. The EEG during cue-based simple imagery (SI), object-oriented motor imagery (OI), non-object-oriented motor imagery (NI) and visual observation (VO) was recorded. Study results showed that OI and NI presented significant contralateral suppression in mu rhythm (p < 0.05). Besides, OI exhibited significant contralateral suppression in beta rhythm (p < 0.05). While no significant mu or beta contralateral suppression could be found during VO or SI (p > 0.05). Compared with NI, OI showed significant difference (p < 0.05) in mu rhythm and weak significant difference (p = 0.0612) in beta rhythm over the contralateral hemisphere. The ability of motor imagery can be reflected by the suppression degree of mu and beta frequencies which are the motor related rhythms. Thus, greater enhancement of activation in mirror neuron system is involved in response to object-oriented motor imagery. The object-oriented motor imagery is favorable for improvement of motor imagery ability.     

Severe Osteogenesis Imperfecta in Cyclophilin B–Deficient Mice

Osteogenesis Imperfecta (OI) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in Prolyl-3-Hydroxylase-1 (LEPRE1). Although P3H1 is known to hydroxylate a single residue (pro-986) in type I collagen chains, it is unclear how this modification acts to facilitate collagen fibril formation. P3H1 exists in a complex with CRTAP and the peptidyl-prolyl isomerase cyclophilin B (CypB), encoded by the Ppib gene. Mutations in CRTAP cause OI in mice and humans, through an unknown mechanism, while the role of CypB in this complex has been a complete mystery. To study the role of mammalian CypB, we generated mice lacking this protein. Early in life, Ppib-/- mice developed kyphosis and severe osteoporosis. Collagen fibrils in Ppib-/- mice had abnormal morphology, further consistent with an OI phenotype. In vitro studies revealed that in CypB–deficient fibroblasts, procollagen did not localize properly to the golgi. We found that levels of P3H1 were substantially reduced in Ppib-/- cells, while CRTAP was unaffected by loss of CypB. Conversely, knockdown of either P3H1 or CRTAP did not affect cellular levels of CypB, but prevented its interaction with collagen in vitro. Furthermore, knockdown of CRTAP also caused depletion of cellular P3H1. Consistent with these changes, post translational prolyl-3-hydroxylation of type I collagen by P3H1 was essentially absent in CypB–deficient cells and tissues from CypB–knockout mice. These data provide significant new mechanistic insight into the pathophysiology of OI and reveal how the members of the P3H1/CRTAP/CypB complex interact to direct proper formation of collagen and bone.     

Desert locusts <Emphasis Type="Italic">Schistocerca gregaria</Emphasis> (Acrididae: Orthoptera) do not lay eggs in old sand: Why?

Schistocerca gregaria sometimes refuse to lay eggs into the “old sand” that is kept in their cages for several days. We investigated why they rejected the old sand for oviposition. Locusts exclusively laid eggs into new sand when presented together with old sand, indicating that the old sand contained an oviposition-inhibiting (OI) factor. We examined whether this factor was derived from locust feces or fed grass (Bromus catharticus). Locusts laid all eggs into the sand with grass when presented together with sand containing feces. In contrast, few eggs were laid into the sand with grass when clean sand was offered at the same time, suggesting that the OI factor originated from the grass and was concentrated in the feces. The OI factor was efficiently extracted from feces with water compared with ethanol and acetone. OI activity was detected by extraction of feces with water for 1 min, although a longer extraction time yielded higher activity. The water extract of feces retained OI activity after boiling. None of the eggs which were buried in sand containing fecal extract hatched, whereas most of the eggs buried in clean sand or sand containing grass extract hatched, showing a correlation between OI activity and a lethal effect on eggs.