O’Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum

BackgroundO’Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O’Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.MethodsAffected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.ResultsWe report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.ConclusionOur study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.

The archbishop’s dinner? Late medieval fish from Esztergom-Várhegy-Kőbánya, Hungary

Fourteenth–fifteenth century food refuse from the kitchen of the Esztergom archbishopric shows a significant diachronic increase in cyprinid bones, in particular those of carp. Meanwhile, contributions by large acipenserids and carnivorous species (catfish/wels, pike, percids) declined. Contemporaneous account books indirectly suggest that the archbishop’s kitchen must have increasingly relied on farmed carp fish. Sturgeons were a commodity sold by the archbishopric but rarely consumed. Expensive pikes were bought at low prices for the archbishop, possibly related to the small size of individuals found in the deposits. The poor representation of high-status fish is consonant with the scarcity of bones from large game in an assemblage dominated by domesticates. Wild game is represented by brown hare, partridge, and a variety of thrushes. These finds confirm that the foodways in the archbishop’s palace were more modest than expected on the basis of its social status. Increasing contributions by cyprinids and sterlet to the assemblage also coincide with the high relative frequency of their recipes in a sixteenth century cookbook.

Identification and Characterization of Human Activation-Induced ChAT+CD4+ T Cells

Vasodilation is a cornerstone of inflammation physiology. By regulating vasodilation and tissue entry of T cells, CD4+ T lymphocytes expressing choline acetyltransferase (ChAT), a key enzyme for biosynthesis of the vasorelaxant acetylcholine (ACh), critically link immunity with vascular biology in mice. However, the characterization of primary human ChAT+ T cells remained elusive. Here, we identified human ChAT+ T cells and report that ChAT mRNA was induced by activation. Functional studies demonstrated that T cell-derived ACh increased muscarinic ACh-receptor dependent NO-synthase activity and vasorelaxation. Further, single-cell RNA-sequencing revealed ChAT+CD4+ T cells in blood from patients with severe circulatory failure and a high relative frequency of ChAT+CD4+ T cells correlated with better 30-day survival in this cohort. Our findings provide the first insights into ChAT biology in primary human T cells, linking ChAT+ T cells with vasorelaxation as well as survival in a cohort of critically ill patients.

Strapdown Attitude Computation: Functional Iterative Integration versus Taylor Series Expansion

There are two basic approaches to strapdown attitude computation, namely, the traditional Taylor series expansion approach and the Picard iterative method. The latter was recently implemented in a recursive form basing on the Chebyshev polynomial approximation and resulted in the so-called functional iterative integration approach. Up to now a detailed comparison of these two approaches with arbitrary number of gyroscope samples has been lacking for the reason that the first one is based on the simplified rotation vector equation while the second one uses the exact form. In this paper, the mainstream algorithms are considerably extended by the Taylor series expansion approach using the exact differential equation and recursive calculation of high-order derivatives, and the functional iterative integration approach is re-implemented on the normal polynomial. This paper applies the two approaches to solve the strapdown attitude problem, using the attitude parameter of quaternion as a demonstration. Numerical results under the classical coning motion are reported to assess all derived attitude algorithms. It is revealed that in the low and middle relative conic frequency range all algorithms have the same order of accuracy, but in the range of high relative frequency the algorithm by the functional iterative integration approach performs the best in both accuracy and robustness if the Chebyshev polynomials and a larger number of gyroscope samples are to be used. The main conclusion applies to other attitude parameters as well.

Morphological relative frequency impedes the use of stylistic variants

The sociolinguistic enterprise has demonstrated that speakers manipulate linguistic variants as they construct their speech style. Contrary to this expectation, this study introduces specific cases in which stylistic variation is highly constrained. We examine the verbal negative suffix in Kansai vernacular Japanese. We first demonstrate that this variable indexes speech style. We then show that in a few specific contexts, such as following the verb stem shir- ‘know’, speakers overwhelmingly use a single variant, in this case, shira-n ‘not know’. We point out that the unusual forms such as shira-n all have a high relative frequency compared to the other forms in their paradigms. Complex forms such as the English word insane, which occur more frequently than their parts (in+sane), are difficult to decompose. We claim that this phenomenon also impedes stylistic variation as forms such as shira-n are not readily decomposed into verb stem + negative suffix.

Relative frequency and the holistic processing of morphology

This study presents apparent-time changes in the morphology of the expression mitai-na ‘similar to’. Based on apparent-time data, we argue that the morphological boundary between mitai and the attributive morpheme -na in the phrase mitai-na has disappeared, and that this complex phrase is now processed as a monomorphemic form. We suggest that relative frequency is the key to understanding the results. We further supplement our argument with data on the standardization of the adverbial adjective form in the Kansai dialect. Young speakers overwhelmingly use the standard form of adverbials for all adjectives except two: yō ‘a lot, well’ and hayō ‘quickly, early’ (instead of Standard Japanese yoku and hayaku). The three linguistic forms that display unusual behavior (mitai-na and the adverbial forms of yō and hayō) all have a high relative frequency. We conclude that when a complex form occurs more frequently than its components (high relative frequency), then it behaves as a monomorphemic unit. The irregular adverbial forms are leftover from an obsolete system, in the same way that many English irregular past forms are leftover from the Germanic strong verb system. In contrast, the irregular form mitai-na emerged from and competes with the regular inflection paradigm for mitai, illustrating a previously undocumented path for the diachronic emergence of irregular morphology.

Pengaruh Pengelolaan Hutan Produksi terhadap Keragaman Jenis Plasma Nutfah Perairan

<p>Management of forest production by application of Reduced Impact Logging (RIL) created crown opening by 13.3%, which was smaller compared with Conventional Logging (CNV) that caused crown opening by19.2%, and provided significant influence to water biodiversity. Availability of nutrient and essential minerals was better in RIL that was supported by high soluble residual or 95% higher and low velocity of river flow or 50% of surrounding CNV water. This physical condition showed significant difference to N and P ratio (N/P ratio) in RIL and CNV or 77.5 and 51.3. These values showed high content of nitrate of the water and it was in oligotropic type condition. Diversity Index of plankton in RIL was 1.754 and in CNV was 1.682 with each population density was 12,916 and 7,222 individuals/liter. The number of plankton had possitive correlation with N/P ratio (r = 0.9). In water catchment study area, there were found 28 fish species belonged to 20 genera and 8 families. The dominance families were Cyprinidae 57.14%, Bagridae 17.14%, and Anguillidae 7.14%. Most endemic fish species of Borneo were also found in both RIL and CNV water, however species with high relative frequency and density were found higher in RIL water.</p><p> </p><p><strong>Abstrak</strong></p><p>Pengelolaan hutan produksi dengan model penebangan Reduced Impact Logging (RIL) membuat pembukaan tajuk seluas 13,3% yang relatif lebih kecil dibandingkan dengan penebangan konvensional (CNV) dengan pembukaan tajuk seluas 19,2%, memberikan pengaruh yang berbeda terhadap keanekaragaman hayati perairan. Ketersediaan nutrisi dan hara penting yang lebih baik di perairan kawasan RIL ditunjang oleh tingginya residu terlarut 95% dan rendahnya kecepatan aliran air sungai 50% dari perairan sekitar CNV. Kondisi fisik perairan yang demikian menunjukkan perbedaan nyata terhadap perbandingan nitrat dan fosfat (N/P rasio) di RIL dan CNV, yaitu 77,5 dan 51,3. Nilai ini menunjukkan kadar nitrat perairan yang tinggi, dan perairan berada dalam tipe oligotropic. Indeks keragaman jenis plankton di RIL 1,754 dan di CNV 1,682 dengan populasi masing-masing 12.916 individu/liter dan 7.222 individu/ liter. Jumlah plankton ini berkorelasi positif dengan N/P rasio (r = 0,9). Di perairan sekitar DAS areal penelitian terdapat 28 jenis ikan tergolong kedalam 20 genera dan 8 famili. Famili dominan adalah Cyprinidae 57,14%, Bagridae 17,14%, dan Anguillidae 7,14%. Sebagian besar ikan jenis endemik Kalimantan terdapat pula di kedua perairan RIL dan CNV, tetapi jenis yang mempunyai kerapatan dan frekuensi relatif tinggi ditemukan lebih banyak di perairan RIL.</p>

Identifying term candidates through adjective–noun constructions in English

This paper evaluates the possibilities of recognizing term candidates through their formal and semantic characteristics. From a cognitive-linguistic stance, the semantic motivation of the word-formation patterns of collocations and compounds in domain-specific texts is assumed to promote their termhood. The semantic motivation to integrate into a multi-word unit is assumed to originate in the generally agreed on generic reference of the modifying constituent. This hypothesis is investigated empirically in a corpus-linguistic experiment. Term candidates instantiating different derivational patterns of adjective–noun constructions have been manually sorted by experts into approved and non-approved terms. Our subsequent linguistic categorization into the morpho-semantic constructions instantiated by the term candidates could be verified quantitatively in terms of relative frequencies. These frequencies clearly divide the term candidates into instances of term-promoting and term-impeding constructions. Obviously, the experts have approved the terms of those constructions which come up with a high relative frequency in the corpus.

Using Multi-Dimensional Credibility to Estimate Class Frequency Vectors in Workers Compensation

The US workers compensation system is different from those in many countries, but it is reinsured in the world-wide market and so has international impact. From its origin in the early 20th century it has been a laboratory for actuarial credibility techniques. In recent years deductibles have been increasing, so that fairly high excess coverage is now commonplace. This puts growing emphasis on estimation of the percentage of loss that is excess of high deductibles. A key element of the excess percentage is the frequency of loss by injury type. Fatalities and permanent disabilities cost more than other injury types, so when they have high relative frequency, more of the claims cost arises from large losses. The vector of claim frequency by injury type can be estimated by class of business using multi-dimensional credibility techniques. Historically the fraction of costs excess of various retentions has been calculated for large groups of classes (hazard groups) and not individual classes. We show, by testing a hold-out sample, that credibility estimation by class does produce additional information in comparison to a widely-used seven-hazard-group system.