Modelling hCDKL5 heterologous expression in bacteria

hCDKL5 refers to the human cyclin-dependent kinase like 5 that is primarily expressed in the brain. Mutations in its coding sequence are often causative of hCDKL5 deficiency disorder, a devastating neurodevelopmental disorder currently lacking a cure. The large-scale recombinant production of hCDKL5 is desirable to boost the translation of preclinical therapeutic approaches into the clinic. However, this is hampered by the intrinsically disordered nature of almost two-thirds of the hCDKL5 sequence, making this region more susceptible to proteolytic attack, and the observed toxicity when the enzyme is accumulated in the cytoplasm of eukaryotic host cells. The bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) is the only prokaryotic host in which the full-length production of hCDKL5 has been demonstrated. To date, a system-level understanding of the metabolic burden imposed by hCDKL5 production is missing, although it would be crucial for upscaling of the production process. Here, we combined experimental data on protein production and nutrients assimilation with metabolic modelling to infer the global consequences of hCDKL5 production in PhTAC125 and to identify potential overproduction targets. Our analyses showed a remarkable accuracy of the model in simulating the recombinant strain phenotype and also identified priority targets for optimised protein production

Personality, gender, and age in the language of social media: the open-vocabulary approach

We analyzed 700 million words, phrases, and topic instances collected from the Facebook messages of 75,000 volunteers, who also took standard personality tests, and found striking variations in language with personality, gender, and age. In our open-vocabulary technique, the data itself drives a comprehensive exploration of language that distinguishes people, finding connections that are not captured with traditional closed-vocabulary word-category analyses. Our analyses shed new light on psychosocial processes yielding results that are face valid (e.g., subjects living in high elevations talk about the mountains), tie in with other research (e.g., neurotic people disproportionately use the phrase ‘sick of’ and the word ‘depressed’), suggest new hypotheses (e.g., an active life implies emotional stability), and give detailed insights (males use the possessive ‘my’ when mentioning their ‘wife’ or ‘girlfriend’ more often than females use ‘my’ with ‘husband’ or 'boyfriend’). To date, this represents the largest study, by an order of magnitude, of language and personalit

Pituitary insufficiency after operation of supratentorial intra- and extraaxial tumors outside of the sellar–parasellar region?

Recent studies investigating pituitary function after non-sellar brain tumor surgery showed that up to 38.2% of patients have pituitary insufficiency (PI). It has been assumed that the operation causes the PI, but preoperative hormone testing, which would have been necessary to prove this assumption, was not performed. The objective of this study is to answer the question if indeed microsurgery is the culprit of PI in patients with operatively treated non-sellar brain tumors. In this prospective trial, 54 patients with supratentorial non-sellar tumors were included. The basal levels of cortisol, prolactin, testosterone, estrogen, IGF-1, fT3, fT4, STH, TSH, ACTH, FSH, and LH were recorded preoperatively on days 1 and 7 after surgery. If basal hormone screening revealed an abnormality, a releasing hormone assay was performed. Before surgery, 24 of the 54 patients (44.4%) already had PI. Additional 25 patients showed either hypocortisolism or hypothyreoidism. As those patients had been pre-treated with dexamethasone and l-thyroxine, these findings were considered not to represent PI but drug effects. Hormone testing on days 1 and 7 after surgery revealed no changes. With 44.4% PI is a frequent finding in brain tumor patients already before surgery. The factors causing preoperative PI remain yet to be identified. The endocrine results after surgery are unchanged which rules out that surgery is the cause of PI

Personality, gender, and age in the language of social media: the open-vocabulary approach

We analyzed 700 million words, phrases, and topic instances collected from the Facebook messages of 75,000 volunteers, who also took standard personality tests, and found striking variations in language with personality, gender, and age. In our open-vocabulary technique, the data itself drives a comprehensive exploration of language that distinguishes people, finding connections that are not captured with traditional closed-vocabulary word-category analyses. Our analyses shed new light on psychosocial processes yielding results that are face valid (e.g., subjects living in high elevations talk about the mountains), tie in with other research (e.g., neurotic people disproportionately use the phrase ‘sick of’ and the word ‘depressed’), suggest new hypotheses (e.g., an active life implies emotional stability), and give detailed insights (males use the possessive ‘my’ when mentioning their ‘wife’ or ‘girlfriend’ more often than females use ‘my’ with ‘husband’ or 'boyfriend’). To date, this represents the largest study, by an order of magnitude, of language and personalit

Consensus on the role of human cytomegalovirus in glioblastoma

The human cytomegalovirus (HCMV) and glioma symposium was convened on April 17, 2011 in Washington, DC, and was attended by oncologists and virologists involved in studying the relationship between HCMV and gliomas. The purpose of the meeting was to reach a consensus on the role of HCMV in the pathology of gliomas and to clarify directions for future research. First, the group summarized data that describe how HCMV biology overlaps with the key pathways of cancer. Then, on the basis of published data and ongoing research, a consensus was reached that there is sufficient evidence to conclude that HCMV sequences and viral gene expression exist in most, if not all, malignant gliomas, that HCMV could modulate the malignant phenotype in glioblastomas by interacting with key signaling pathways; and that HCMV could serve as a novel target for a variety of therapeutic strategies. In summary, existing evidence supports an oncomodulatory role for HCMV in malignant gliomas, but future studies need to focus on determining the role of HCMV as a glioma-initiating event