Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel homozygous TPM1 mutation in familial pediatric hypertrophic cardiomyopathy and in silico screening of potential targeting drugs.

OBJECTIVE Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. While sarcomeric gene mutations explain many HCM cases, the genetic basis of about half of HCM cases remains elusive. Here we aimed to identify the gene causing HCM in a non-consanguineous Saudi Arabian family with affected family members and a history of sudden death. The impact of the identified mutation on protein structure and potential drug targets were evaluated in silico. MATERIALS AND METHODS Triplets (two HCM subjects and one patent ductus arteriosus (PDA) case) and unaffected parents were screened by targeted next-generation sequencing (NGS) for 181 candidate cardiomyopathy genes. In silico structural and functional analyses, including protein modeling, structure prediction, drug screening, drug binding, and dynamic simulations were performed to explore the potential pathogenicity of the variant and to identify candidate drugs. RESULTS A homozygous missense mutation in exon 1 of TMP1 (assembly GRCh37-chr15: 63340781; G>A) was identified in the triplets [two HCM and one patent ductus arteriosus (PDA)] that substituted glycine for arginine at codon 3 (p.Gly3Arg). The parents were heterozygous for the variant. The mutation was predicted to cause a significant and deleterious change in the TPM1 protein structure that slightly affected drug binding, stability, and conformation. In addition, we identified several putative TPM1-targeting drugs through structure-based in silico screening. CONCLUSIONS TPM1 mutations are a common cause of HCM and other congenital heart defects. To date, TPM1 has not been associated with isolated PDA; to our knowledge, this is the first report of the homozygous missense variation p.Gly3Arg in TPM1 associated with familial autosomal recessive pediatric HCM and PDA. The identified candidate TPM1 inhibitors warrant further prospective investigation.
Etude De La Receptivite Sexuelle De La Femelle De Calliphora Vomitoria (Dipteres, Calliphoridae) Au Cours Du Premier Cycle Gonadotrope

With both behavioural and physiological parameters we have studied the development of the sexual receptivity in females Calliphora vomitoria during the first gonadotropic cycle. From a behavioural point of view, we have noticed a temporal patterning in the appearance of the maximum attractivity (4 days after emergence), minimum courtship duration (5 days after emergence) and the maximum receptivity (6 days after emergence). The sexual receptivity is correlated with vitellogeny and increases with the growth of the ovaries. It is partly inhibited by precocial ovariectomy (6 hours after emergence) and totally suppressed by allatectomy (3 hours after emergence). A topical application of ZR-515 (1 ul at a 3 ug/ul concentration) induces an anticipative receptivity (1 day) and an acceleration of ovarian growth. We obtained an optimal effect when the application takes place some hours before the beginning of vitellogeny (2 days instead of 3 hours after eclosion). Concentration of roughly 30, 300 and 600 ug/ul have an inhibitory effect upon the sexual receptivity and its associated parameters. The attractivity of females for males is only partly related to their receptivity: it appears early (2 days) for all flies, but it remains always lower in non-receptive mature females compared to receptive mature females. Neither ovariectomy nor allatectomy are able to prevent it to appear, which suggests that JH is not involved in that process.
Role of cyclin-dependent kinase 5 in neurodegenerative disorders

Alzheimer’s disease (AD) is a neurodegenerative confusion associated with dementia. AD is indicated by progressive loss of memory. It is having characteristic evidence of β-amyloid extracellularly and neurofibrillary tangle’s development intracellularly. Neurons lose the capability of cell division after they attain full development. Cyclin dependent kinase 5 (Cdk5) is a kinase protein which is neuron specific and plays a vital role in the movement of newly developed neurons. When Cdk5 is dysregulated, then several diseases like AD, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) may occur. The Cdk5 phosphorylation takes place as a result of change of N-methyl-D-aspartate (NMDA) receptor activity and expression, neurotransmitter release, degradation of synaptic proteins, or in-gene expression modulation, which leads to the activation of Cdk5. The activated calpain proteins convert p35 activator of Cdk5 into p25, which causes remarkable activation of the Cdk5. This highly activates Cdk5-p25 complex hyperphosphorylates, the Tau protein, which causes the release of microtubules and gathers as cytoplasmic filaments. This leads to tangle formation that leads to neuronal cell death. In AD brain, the Cdk5 is present in a highly activated form. This review article emphasizes the role of cyclin dependent kinase 5 in AD. Key words: Alzheimer’s disease, β-amyloid plaques, CDK5, neurodegeneration, neurofibrillary tangle.
Internet NZ study - stage 1 report

Broadband connectivity and the great variety of services offered over the Internet have made it an important source of information and entertainment and a major means of communication. In 2008, users are more connected than ever. With connectivity to the Internet, however, come security threats. Because the Internet is a global network, an attack can be delivered anonymously from any location in the world. In 2003, a study was published that compared vulnerabilities in web servers from various countries. It showed that web sites in the New Zealand domain were one of the most vulnerable to Google hacking attacks. Vulnerable web servers lead to compromised web servers, which do not only pose a risk to operators of these web servers, but also to their users or customers, because the attackers might insert client-side attacks that trigger upon interaction with such a compromised server. As part of work commissioned by InternetNZ, Victoria University of Wellington has gathered intelligence on the threat from malicious servers across different country domains (.au, .com, .nz, and .uk) In this study, it was assessed whether the web servers located in the nz domains would show an elevated percentage of malicious web servers in line with their vulnerability independent by Nehring [4]. Results of this study show malicious URLs in all domains. Inspecting 664,000 URLs, 38 malicious URLs were identified. The majority of these malicious URLs were unknown to providers of security products/ services therefore unable to protect potential end users that visit those URLs. No indications were detected that show an elevated percentage of malicious web servers in the nz domain. Rather, a statistically significant elevated percentage was detected in the au domain compared to any other domain inspected. In the nz domain, three malicious URLs were detected in this study that scanned part of the nz domain. Assuming approximately 4 million web servers exist in the nz domain, the number of malicious web servers is estimated to be in the order of 640 or 0.00016%. In the next stage of this work, all web servers in the nz domain will be inspected to provide a more complete picture of the threat of client-side attacks to New Zealand.
Sexual dimorphism in the reaction of zebrafish (Brachydanio rerio) to ascorbic acid deficiency: Induction of steatosis in hepatocytes of male fish

Summary Zebrafish (Brachydanio rerio) fed diets free of ascorbic acid (vitamin C) or suplemented with 200 mg/kg ascorbic acid for 12 weeks were compared with respect to macroscopically detectable symptoms of pathology and cytoloical alterations of hepatocytes. Fish fed the ascorbic acid-free diet displayed symptoms of scurvy including hemorrhages, fin erosion, and darker pigmentation. Hepatocytes of male zebrafish developed steatosis, whereas liver cells of female zebrafish were free of microvesicular lipid accumulation within the endoplasmic reticulum cisternae, indicating the presence of sex-dependent protection mechanisms against ascorbic acid depletion. Female fish showed a reduction of hepatocellular size and a less regular arrangement of the rough endoplasmic reticulum; hepatocellular glycogen depletion as well as induction of smooth endoplasmic reticulum were characterstic of hepatocytes in either sex. Since zebrafish fed the diet supplemented with ascorbic acid were free of pathological alterations in both external appearance and hepatocellular ultrastructure, results indicate that ascorbic acid not only plays a key role in collagen biosynthesis, but also fulfills central functions in the maintenance of a well-equilibrated lipid metabolism in fish. Accumulation of oxidative reagents represents one possible mechanism leading to hepatocellular steatosis in fish.
Research-Minded Practice With Young Offenders Who Commit Grave Crimes

Gwyneth Boswell presents the key results from her research into Section 53 offenders during the 1990s, which found high levels of abuse and/or loss amongst this unusual group of offenders. She explores the implications for assessment and intervention, arguing that a knowledge of relevant research is an essential prerequisite to focused and effective practice.
Current Account Policies

The effectiveness of tariffs and taxes on foreign borrowing for reducing current account deficits is examined in a two-sector neoclassical optimal growth model of a small open-economy. The outputs of both sectors are tradable, and capital is used in only one sector while labor is employed in both. The dynamics of the current account are modelled over an infinite horizon with an endogenous discount rate. Imposition of a tariff on the capital-using good leads to a current account deficit on impact followed by surpluses as adjustwnt to the steady-state occurs. A tariff placed on the other good leads to surpluses both initially and over time. A tax levied on foreign borrowing also leads to surpluses.
Predicting tree crown ratio for unthinned and thinned Scots pine stands

A nonlinear model that yields logical predictions for tree crown ratio is presented. The model is based on data from permanent experimental plots located in even-aged Scots pine (Pinussylvestris L.) stands in southern and central Finland. Regressor variables in the model are stand dominant height, stand basal area, tree diameter, and tree height. The effect of thinning on tree crown ratio is modelled by incorporating a thinning response variable into the model. Thinning effect is dependent on thinning intensity and time elapsed from thinning, the latter of which is represented by the difference between current stand dominant height and dominant height at the time of thinning.
A Survey of Chemoreceptive Responses on Different Mosquito Appendages

Abstract Research on the functions of insect chemoreceptors have primarily focused on antennae (olfactory receptors) and mouthparts (gustatory receptors). However, chemoreceptive sensilla are also present on other appendages, such as the leg tarsi and the anterior wing margin, and their specific roles in chemoreception and mosquito behavior remain largely unknown. In this study, electrophysiological analyses in an electroantennogram recording format were performed on Aedes aegypti (L., Diptera: Culicidae) antennae, mouthparts, tarsi, and wings during exposure to a variety of insect repellent and attractant compounds. The results provide evidence that the tarsi and wings can sense chemicals in a gaseous form, and that the odors produce differing responses on different appendages. The most consistent and strongest response occurred when exposed to triethylamine (TEA). Antennae and mouthparts showed nearly identical responses pattern to all tested compounds, and their rank orders of effectiveness were similar to those of fore- and mid-leg tarsi. Hindleg tarsi only responded to TEA, indicating that the hind legs are not as chemoreceptive. Wings responded to a range of odorants, but with a different rank order and voltage amplitude. Insights gleaned into the function of these appendages in insect chemoreception are discussed.
Secure Distributed State Estimation for Networked Microgrids

Distributed state estimation (DSE) allows networked microgrids to achieve global state awareness with conservation of local information privacy by peer-to-peer message exchange implemented with Internet of Things protocols over heterogeneous communications. This paper presents a secure DSE (SDSE) method for networked microgrids to enhance system resiliency by addressing false data injection threat in distributed microgrid agent nodes. The designated SDSE applies a trust-based diffusion algorithm using adaptive combination policy, which allows agents to adapt their combination coefficients to exclude misbehaving nodes from the network. The results demonstrate that proposed SDSE algorithm addresses emerging data integrity and security problems in critical energy delivery infrastructure and SCADA environment.
Denitrification in freshwater and coastal marine ecosystems: Ecological and geochemical significance

Denitrification occurs in essentially all river, lake, and coastal marine ecosystems that have been studied. In general, the range of denitrification rates measured in coastal marine sediments is greater than that measured in lake or river sediments. In various estuarine and coastal marine sediments, rates commonly range between 50 and 250 µmol N m−2 h−1, with extremes from 0 to 1,067. Rates of denitrification in lake sediments measured at near-ambient conditions range from 2 to 171 µmol N m−2 h−1. Denitrification rates in river and stream sediments range from 0 to 345 µmol N m−2 h−1. The higher rates are from systems that receive substantial amounts of anthropogenic nutrient input. In lakes, denitrification also occurs in low oxygen hypolimnetic waters, where rates generally range from 0.2 to 1.9 µmol N liter−1 d−1. In lakes where denitrification rates in both the water and sediments have been measured, denitrification is greater in the sediments. The major source of nitrate for denitrification in most river, lake, and coastal marine sediments underlying an aerobic water column is nitrate produced in the sediments, not nitrate diffusing into the sediments from the overlying water. During the mineralization of organic matter in sediments, a major portion of the mineralized nitrogen is lost from the ecosystem via denitrification. In freshwater sediments, denitrification appears to remove a larger percentage of the mineralized nitrogen. N2 fluxes accounted for 76–100% of the sediment-water nitrogen flux in rivers and lakes, but only 15–70% in estuarine and coastal marine sediments. Benthic N2O fluxes were always small compared to N, fluxes. The loss of nitrogen via denitrification exceeds the input of nitrogen via N2 fixation in almost all river, lake, and coastal marine ecosystems in which both processes have been measured. Denitrification is also important relative to other inputs of fixed N in both freshwater and coastal marine ecosystems. In the two rivers where both denitrification measurements and N input data were available, denitrification removed an amount of nitrogen equivalent to 7 and 35% of the external nitrogen loading. In six lakes and six estuaries where data are available, denitrification is estimated to remove an amount of nitrogen equivalent to between 1 and 36% of the input to the lakes and between 20 and 50% of the input to the estuaries.
Ceremonial Gatherings of the Magpie Pica Pica: Territory Probing and Acquisition

During a seven year study of magpie social organisation we collected data to examine the idea that 'ceremonial gatherings' were associated with territory acquisition. Gatherings were initiated by high ranking, non-territorial birds, mainly in the three months prior to the breeding season. Most gatherings resulted in initiators being evicted, but in some cases they obtained a territory, either by displacing the owners, or by repeatedly visiting the same area and establishing a territory of their own, usually on territory boundaries where resistance from established birds was least. About 30% of territories were acquired via gatherings. The various ways in which other long-term territorial species acquire territories are discussed.
TNFα suppresses link protein and type II collagen expression in chondrocytes: Role of MEK1/2 and NF‐κB signaling pathways

Tumor necrosis factor α (TNFα) inhibits matrix synthesis by chondrocytes in rheumatoid arthritis and osteoarthritis; however, the underlying signaling pathways are poorly characterized. This study investigated the TNFα‐activated pathways regulating expression of two key components of the cartilage matrix—link protein and type II collagen. In rat articular chondrocytes, TNFα decreased link protein and type II collagen mRNA to undetectable levels within 48 h. Levels of link protein mRNA recovered more readily than type II collagen mRNA following removal of the cytokine. TNFα‐mediated reduction in mRNA of both matrix molecules occurred at the level of transcription and, for link protein, mRNA stability. Turnover of type II collagen and link protein mRNA was dependent on new protein synthesis. In both prechondrocytes and articular chondrocytes, TNFα induced concentration‐dependent activation of MEK1/2 and NF‐κB, but not p38 or JNK. Sustained activation of NF‐κB was observed for up to 72 h following continuous or transient exposure to TNFα. Using pharmacological and molecular approaches, the MEK1/2 and NF‐κB pathways were found to mediate inhibition of type II collagen and link protein gene expression by TNFα. Both prechondrocytes and articular chondrocytes are targets of TNFα. This study identifies pathways through which TNFα perturbs the synthesis and organization of articular cartilage matrix during inflammation. J. Cell. Physiol. 197: 357–369, 2003© 2003 Wiley‐Liss, Inc.
Metastatic Ameloblastoma to the Liver: Rare Presentation of a Rare Disease

Ameloblastoma is a slow growing odontogenic epithelial neoplasm which originates from remnants of the dental lamina with a high recurrence rate, but a low tendency to metastasize. Locally invasive ameloblastoma is often aggressive and destructive, which erodes bone and invades adjacent structures. Despite a benign histology metastatic disease may occur and samples taken from metastatic tumor usually maintains the features of the original tumor. Ameloblastic carcinoma differs from ameloblastoma with malignant cytological features. Here we report an unusual case of ameloblastoma metastatic to lung and liver, unresponsive to systemic treatment with cisplatin and adriamycin, and well controlled with local surgical treatment. *Corresponding author: Lacin S, Department of Medical Oncology, Hacettepe Cancer Institute, Hacettepe University Sıhhiye Campus, Oncology Hospital 2nd Floor, Altındag, Turkey, Tel: +905321591069; E-mail: sahin81lacin@yahoo.com Received January 20, 2019; Accepted January 29, 2019; Published January 31, 2019 Citation: Lacin S, Dogrul A, Dikmen E, Kertmen N, Turker A, et al. (2019) Metastatic Ameloblastoma to the Liver: Rare Presentation of a Rare Disease. J Clin Case Rep 9: 1207. doi: 10.4172/2165-7920.10001207 Copyright: © 2019 Lacin S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Childhood survivors of high‐risk neuroblastoma show signs of immune recovery and not immunosenescence

Neuroblastoma survivors show signs of immunosenescence early after therapy in CD8+ T cell compartment and elevated plasma TNF‐α but in later follow‐up immune recovery comes into play. Whether the recovery phenotype is long lasting or transient remains to be elucidated, however, late adverse effects often occur in childhood cancer survivors.
Intraindividual double burden of overweight or obesity and micronutrient deficiencies or anemia among women of reproductive age in 17 population-based surveys

Background: Rising prevalence of overweight/obesity (OWOB) alongside persistent micronutrient deficiencies suggests many women face concomitant OWOB and undernutrition. Objectives: We aimed to 1) describe the prevalence of the double burden of malnutrition (DBM) among nonpregnant women of reproductive age, defined as intraindividual OWOB and either ≥1 micronutrient deficiency [micronutrient deficiency index (MDI) > 0; DBM-MDI] or anemia (DBM-anemia); 2) test whether the components of the DBM were independent; and 3) identify factors associated with DBM-MDI and DBM-anemia. Methods: With data from 17 national surveys spanning low- and middle-income countries (LMICs) and high-income countries from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project (n = 419 to n = 9029), we tested independence of over- and undernutrition using the Rao–Scott chi-square test and examined predictors of the DBM and its components using logistic regression for each survey. Results: Median DBM-MDI was 21.9% (range: 1.6%–39.2%); median DBM-anemia was 8.6% (range: 1.0%–18.6%). OWOB and micronutrient deficiencies or anemia were independent in most surveys. Where associations existed, OWOB was negatively associated with micronutrient deficiencies and anemia in LMICs. In 1 high-income country, OWOB women were more likely to experience micronutrient deficiencies and anemia. Age was consistently positively associated with OWOB and the DBM, whereas the associations with other sociodemographic characteristics varied. Higher socioeconomic status tended to be positively associated with OWOB and the DBM in LMICs, whereas in higher-income countries the association was reversed. Conclusions: The independence of OWOB and micronutrient deficiencies or anemia within individuals suggests that these forms of over- and undernutrition may have unique etiologies. Decision-makers should still consider the prevalence, consequences, and etiology of the individual components of the DBM as programs move towards double-duty interventions aimed at addressing OWOB and undernutrition simultaneously.
Reduced photorespiration and increased energy‐use efficiency in young CO2‐enriched sorghum leaves

Summary • To determine the response of C4 plants to elevated CO2 it is necessary to establish whether young leaves have a fully developed C4 photosynthetic apparatus, and whether photosynthesis in these leaves is responsive to elevated CO2. • The effect of free-air CO2 enrichment (FACE) on the photosynthetic development of the C4 crop Sorghum bicolor was monitored. Simultaneous measurements of chlorophyll a fluorescence and carbon assimilation were made to determine energy utilization, quantum yields of carbon fixation (φCO2) and photosystem II (φPSII), as well as photorespiration. • Assimilation in the second leaf of FACE plants was 37% higher than in control plants and lower apparent rates of photorespiration at growth CO2 concentrations were exhibited. In these leaves, φPSII : φCO2 was high at low atmospheric CO2 concentration (Ca) due to overcycling of the C4 pump and increased leakiness. As Ca increased, φPSII : φCO2 decreased as a greater proportion of energy derived from linear electron transfer was used by the C3 cycle. • The stimulation of C4 photosynthesis at elevated Ca in young leaves was partially due to suppressed photorespiration. Additionally, elevated Ca enhanced energy-use efficiency in young leaves, possibly by decreasing CO2 leakage from bundle sheath cells, and by decreasing overcycling of the C4 pump.