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Kankana-ey is a widely used dialect in the northern region of the Philippines. Unfortunately, there are documented studies on the syntactic rules of this dialect. This study explored the development of a corpus for the Kankana-ey dialect. Further, the corpus was then used to establish the syntactic rules of Kankana-ey. A Kankana-ey version of the bible, dictionaries, news articles, songs and various online resources were used to collect words for the corpus of the Kankana-ey dialect. These identified words were also tagged using the parts of speech tags of the Penn TreeBank. Using the corpus and TensorFlow, 320 Kankana-ey sentences were analysed to determine the syntactic rules. In addition, 80 sentences were used to test the accuracy of the identified rules. At the end of the study, the created corpus has 3,412 tagged Kankana-ey words, while the analysis of the syntactic rules resulted to 1,722 rules. Testing also showed a 60% accuracy of the syntactic rules. In conclusion, the high number of identified rules from the 320 sentences was due to multiple Kankana-ey words having different possible tags. This also resulted to the low accuracy of the syntactic rules.

NKX2-5 is a homeodomain-containing transcription factor implied in both heart and thyroid development. Numerous mutations in NKX2-5 have been reported in individuals with congenital heart disease (CHD), but recently a select few have been associated with thyroid dysgenesis, among which the p.A119S variation. We sequenced NKX2-5 in 303 sporadic CHD patients and 38 families with at least two individuals with CHD. The p.A119S variation was identified in two unrelated patients: one was found in the proband of a family with four affected individuals with CHD and the other in a sporadic CHD patient. Clinical evaluation of heart and thyroid showed that the mutation did not segregate with CHD in the familial case, nor did any of the seven mutation carriers have thyroid abnormalities. We tested the functional consequences of the p.A119S variation in a cellular context by performing transactivation assays with promoters relevant for both heart and thyroid development in rat heart derived H10 cells and HELA cells. There was no difference between wildtype NKX2-5 and p.A119S NKX2-5 in activation of the investigated promoters in both cell lines. Additionally, we reviewed the current literature on the topic, showing that there is no clear evidence for a major pathogenic role of NKX2-5 mutations in thyroid dysgenesis. In conclusion, our study demonstrates that p.A119S does not cause CHD or TD and that it is a rare variation that behaves equal to wildtype NKX2-5. Furthermore, given the wealth of published evidence, we suggest that NKX2-5 mutations do not play a major pathogenic role in thyroid dysgenesis, and that genetic testing of NKX2-5 in TD is not warranted.

Kawasaki disease is an acute vasculitis of possible infectious cause, which in particular affects the coronary arteries. Young children rely mostly on their innate immune system for protection against invading microorganisms, of which mannose-binding lectin is an important component. We aimed to investigate the possible role of the gene for this molecule ( MBL) in white Dutch patients with Kawasaki disease. In 90 patients, frequency of mutations in the MBL gene was higher than in healthy children. In children younger than 1 year, those with mutations were at higher risk of development of coronary artery lesions than were those without (odds ratio 15–7, 95% CI 1·4–176·5, p=0·026). Our findings suggest that the innate immune system contributes differently to pathophysiology of Kawasaki disease at various ages.

Congenital heart defects (CHDs) occur mostly sporadic, but familial CHD cases have been reported. Mutations in several genes, including NKX2.5, GATA4 and NOTCH1, were identified in families and patients with CHD, but the mechanisms underlying CHD are largely unknown. We performed genome-wide linkage analysis in a large four-generation family with autosomal dominant CHD (including atrial septal defect type I and II, tetralogy of Fallot and persistent left superior vena cava) and low atrial rhythm, a unique phenotype that has not been described before. We obtained phenotypic information including electrocardiography, echocardiography and DNA of 23 family members. Genome-wide linkage analysis on 12 affected, 5 unaffected individuals and 1 obligate carrier demonstrated significant linkage only to chromosome 9q21–33 with a multipoint maximum LOD score of 4.1 at marker D9S1690, between markers D9S167 and D9S1682. This 48-c M critical interval corresponds to 39 Mb and contains 402 genes. Sequence analysis of nine candidate genes in this region ( INVS , TMOD1 , TGFBR1 , KLF4 , IPPK , BARX1 , PTCH1 , MEGF9 and S1PR3 ) revealed no mutations, nor were genomic imbalances detected using array comparative genomic hybridization. In conclusion, we describe a large family with CHD and low atrial rhythm with a significant LOD score to chromosome 9q. The phenotype is representative of a mild form of left atrial isomerism or a developmental defect of the sinus node and surrounding tissue. Because the mechanisms underlying CHD are largely unknown, this study represents an important step towards the discovery of genes implied in cardiogenesis.

Data on the prevalence of congenital heart defects (CHD) in neuroblastoma patients are inconsistent. If CHD are more common in neuroblastoma patients than in the general population, cardiac screening might be warranted. In this study we used echocardiography to determine the prevalence of CHD in a single centre cohort of surviving neuroblastoma patients. In addition, we performed a systematic review of the literature. Echocardiography was performed in 119 of 133 patients (89.5%). Only two patients (1.7%) had CHD. The prevalence of CHD was not significantly different from a previously published control group of 192 leukaemia patients examined by echocardiography ( P  = 0.49). Literature search revealed 17 studies, showing prevalence rates of CHD in neuroblastoma patients ranging from 0 to 20%. Prevalence was less than 3.6% in the majority of studies. Most studies lacked information on validity. We conclude that current evidence does not support standard cardiac screening in all patients with neuroblastoma.

Kuijpers et al discuss the case of a two-year-old boy who was admitted to the hospital with chickenpox. The skin on his fingers began to peel following treatment. He was diagnosed with Kawasaki's disease.

Key Points Forkhead box (FOX) proteins are a superfamily of transcriptional regulators that have a key role both during development and in adult tissue homeostasis. Fifty human FOX proteins related through their 'forkhead' or 'winged-helix' DNA-binding domain (DBD) have been discovered, and they are further divided into 19 subfamilies (FOXA to FOXS) on the basis of sequence homology within and outside their forkhead domain. Forkhead transcription factors, in particular FOXA, FOXC, FOXM, FOXO and FOXP proteins, are essential components of oncogenic and tumour suppressive pathways. Deregulation of FOX proteins has a direct role in cancer initiation, maintenance, progression and drug resistance. Control of various FOX family members is not only achieved through cell-specific expression, but is also fine-tuned by a myriad of post-translational modifications and through interactions with specific cofactors. Besides being conventional transcriptional activators, FOX proteins also function as transcriptional repressors, pioneer factors, and they modulate and cooperate with other transcription factors and epigenetic effectors. A better understanding of the mechanistic complexities that govern the regulation and functions of these FOX transcription factors should help us to realize their potential as therapeutic targets, as well as reliable predictive markers for cancer. Forkhead box (FOX) transcription factors fine-tune the spatial and temporal expression of many genes and integrate a multitude of cellular and environmental signals. Several FOX family transcription factors have been implicated in cancer and may be therapeutic targets or putative biomarkers. Forkhead box (FOX) proteins are multifaceted transcription factors that are responsible for fine-tuning the spatial and temporal expression of a broad range of genes both during development and in adult tissues. This function is engrained in their ability to integrate a multitude of cellular and environmental signals and to act with remarkable fidelity. Several key members of the FOXA, FOXC, FOXM, FOXO and FOXP subfamilies are strongly implicated in cancer, driving initiation, maintenance, progression and drug resistance. The functional complexities of FOX proteins are coming to light and have established these transcription factors as possible therapeutic targets and putative biomarkers for specific cancers.

The binding of cytoplasmic Ca 2+ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck of an hourglass-shaped pore. By combining mutagenesis, electrophysiology, and cryo-electron microscopy, we identified three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate. Mutation of each of these residues increases the potency of Ca 2+ and results in pronounced basal activity. The structure of an activating mutant shows a conformational change of an α-helix that contributes to Ca 2+ binding as a likely cause for the basal activity. Although not in physical contact, the three residues are functionally coupled to collectively contribute to the stabilization of the gate in the closed conformation of the pore, thus explaining the low open probability of the channel in the absence of Ca 2+ . The binding of cytoplasmic Ca 2+ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck. Here authors use cryo-EM and electrophysiology to identify three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate.

We used magnetoencephalography (MEG) to explore the spatiotemporal dynamics of neural oscillations associated with sentence processing in 102 participants. We quantified changes in oscillatory power as the sentence unfolded, and in response to individual words in the sentence. For words early in a sentence compared to those late in the same sentence, we observed differences in left temporal and frontal areas, and bilateral frontal and right parietal regions for the theta, alpha, and beta frequency bands. The neural response to words in a sentence differed from the response to words in scrambled sentences in left-lateralized theta, alpha, beta, and gamma. The theta band effects suggest that a sentential context facilitates lexical retrieval, and that this facilitation is stronger for words late in the sentence. Effects in the alpha and beta bands may reflect the unification of semantic and syntactic information, and are suggestive of easier unification late in a sentence. The gamma oscillations are indicative of predicting the upcoming word during sentence processing. In conclusion, changes in oscillatory neuronal activity capture aspects of sentence processing. Our results support earlier claims that language (sentence) processing recruits areas distributed across both hemispheres, and extends beyond the classical language regions. •Words in a sentence induce left-lateralized oscillatory responses at θ, α, β, and γ.•Unfolding sentence context modulates θ, α, and β oscillations in both hemispheres.•Oscillations source-localize to regions in line with earlier fMRI and M/EEG studies.•Effects suggest lexical retrieval, unification, attention, and prediction processes.