Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy

Histone deacetylase (HDAC)-inhibitors (HDACis) are well characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant cells while sparing normal cells. Gene expression-based chemical genomics identified HDACis as being particularly potent against Down syndrome associated myeloid leukemia (DS-AMKL) blasts. Investigating the anti-leukemic function of HDACis revealed their transcriptional and posttranslational regulation of key autophagic proteins, including ATG7. This leads to suppression of autophagy, a lysosomal degradation process that can protect cells against damaged or unnecessary organelles and protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mTOR activation. Consequently, HDAC inhibition repressed autophagy below a critical threshold, which resulted in accumulation of mitochondria, production of reactive oxygen species, DNA-damage and apoptosis. Those HDACi-mediated effects could be reverted upon autophagy activation or aggravated upon further pharmacological or genetic inhibition. Our findings were further extended to other major acute myeloid leukemia subgroups with low basal level autophagy. The constitutive suppression of autophagy due to mTOR activation represents an inherent difference between cancer and normal cells. Thus, via autophagy suppression, HDACis deprive cells of an essential pro-survival mechanism, which translates into an attractive strategy to specifically target cancer cells

The Developing Human Connectome Project Neonatal Data Release

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed

The bear in Eurasian plant names: Motivations and models

Ethnolinguistic studies are important for understanding an ethnic group's ideas on the world, expressed in its language. Comparing corresponding aspects of such knowledge might help clarify problems of origin for certain concepts and words, e.g. whether they form common heritage, have an independent origin, are borrowings, or calques. The current study was conducted on the material in Slavonic, Baltic, Germanic, Romance, Finno-Ugrian, Turkic and Albanian languages. The bear was chosen as being a large, dangerous animal, important in traditional culture, whose name is widely reflected in folk plant names. The phytonyms for comparison were mostly obtained from dictionaries and other publications, and supplemented with data from databases, the co-authors' field data, and archival sources (dialect and folklore materials). More than 1200 phytonym use records (combinations of a local name and a meaning) for 364 plant and fungal taxa were recorded to help find out the reasoning behind bear-nomination in various languages, as well as differences and similarities between the patterns among them. Among the most common taxa with bear-related phytonyms were Arctostaphylos uva-ursi (L.) Spreng., Heracleum sphondylium L., Acanthus mollis L., and Allium ursinum L., with Latin loan translation contributing a high proportion of the phytonyms. Some plants have many and various bear-related phytonyms, while others have only one or two bear names. Features like form and/or surface generated the richest pool of names, while such features as colour seemed to provoke rather few associations with bears. The unevenness of bear phytonyms in the chosen languages was not related to the size of the language nor the present occurence of the Brown Bear in the region. However, this may, at least to certain extent, be related to the amount of the historical ethnolinguistic research done on the selected languages

Chapter 2. A new bilingual votive monument with a “Thracian rider” relief

The monument that we present here in honor of Stephen Tracy exhibits a votive relief of the “Thracian rider” type and a bilingual Greek and Latin dedication by a certain Felicio, slave of Gaius Menanius. Physical Description Votive monument of white marble, preserved on all sides, rough-picked in back. The relief above the inscription shows a horse and a rider facing a snake-entwined tree on the right; the rider is dressed in a chlamys, which lies flat on his back; he is holding a round pater..

Acute viral infection encephalopathy linked to organic personality disorder

Introduction: Encephalopathy is a structural and/or functional disorder of the brain with multiple causes, one of them being acute viral infection. It is clinically presented with a variety of neurologi­cal and psychiatric symptoms - muscle weakness, poor concentration, seizures, changes in personal­ity, as well as lethargy or psychosis.Materials and methods: A 12-year-old patient is being presented, hospitalized in the past due to viral encephalitis. Symptoms included fever, nausea, drowsiness, apathy and confusion. A lumbar punc­ture was performed at the time with no pathogens found in the cerebrospinal fluid. After a psychi­atric assessment through an interview the patient was diagnosed with organic personality disorder. Therapy was conducted and after the full resolution of the patient`s condition he was discharged. An year and a half later a relapse of previous symptomatology occurred. The boy was hospitalized again in a psychosis-like state after an interview with a psychiatrist.Results: Beginning with fever the second episode included visual hallucinations, photophobia and disorientation, psychosis-like beliefs - believing his mother is not real (Capgras syndrome). Although fully managing the first episode a therapy with Aripiprazole and Finlepsin only lead to a partial im­provement and fluctuation of the condition during the relapse. A follow up and additional examina­tions were commissioned.Conclusion: Even though long term complications are rare the condition should be treated with care. Neuropsychiatric symptoms are common in the acute phase of viral encephalitis. In rare cas­es they may also reappear after recovery, especially in children. Symptoms may present as psychosis (35%), catatonia (33%), psychotic depression (16%), and mania (11%). Post-infectious structural and functional changes in the brain may lead to personality shifts, e.g. detachment from reality and dis­inhibited behaviour resulting in long-term disability and social isolation of the patient. Psychiatric consultation and follow-up should be requested for patients at risk without hesitation

The role of videofluoroscopic swallow examination after total laryngectomy

Introduction: Laryngectomy (LE) is a standard procedure for the treatment of advanced laryngeal malignancies. Laryngeal extirpation is followed by the placement of a nasogastric tube (NGT), sutur­ing of the pharyngeal defect and forming of a tracheal stoma. In the early postoperative period a vid­eo fluoroscopic swallowing exam (VFSE) may be performed in an attempt to evaluate the pharyngeal reconstruction and the swallowing function.Materials and methods: VFSE includes preparation of the contrast agent, specific positioning of the patient and capturing of series of x-ray images. The oral agent, used in VFSE is a non-ionic water sol­uble contrast. During the examination the patient is placed in a lateral position in order to examine all swallowing phases and to detect abnormalities. The act of swallowing includes 3 phases: oral, pha­ryngeal and esophageal. Defects can be observed in each one of these phases.Results: Dysphagia is the most common complication in patients after total LE. This symptom has a number of causes - early postoperative insufficiency of the plasty, pharyngeal dysmotility, develop­ment of a stricture, pseudo-diverticulum, pharyngocutaneous fistulas or recurrence of the cancer.Conclusion: The VFSE results give information about the types of esophageal dysphagia after total LE. According to the data from the VFSE a decision can be taken whether to remove the NGT and start oral feeding, or leave it in place, in case of suspected insufficiency. The videofluoroscopic aspect of the defect may help for the selection of an appropriate treatment: operative or conservative. All these factors are important for the duration of the hospital stay