Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay

The transcriptome in a cell is finely regulated by a large number of molecular mechanisms able to control the balance between mRNA production and degradation. Recent experimental findings have evidenced that fine and specific regulation of degradation is needed for proper orchestration of a global cell response to environmental conditions. We developed a computational technique based on stochastic modeling, to infer condition-specific individual mRNA half-lives directly from gene expression time-courses. Predictions from our method were validated by experimentally measured mRNA decay rates during the intraerythrocytic developmental cycle of Plasmodium falciparum. We then applied our methodology to publicly available data on the reproductive and metabolic cycle of budding yeast. Strikingly, our analysis revealed, in all cases, the presence of periodic changes in decay rates of sequentially induced genes and co-ordination strategies between transcription and degradation, thus suggesting a general principle for the proper coordination of transcription and degradation machinery in response to internal and/or external stimuli. Citation: Cacace F, Paci P, Cusimano V, Germani A, Farina L (2012) Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay. PLoS Comput Biol 8(11): e1002772. doi:10.1371/journal.pcbi.100277

Prevalence and predictors of left ventricular hypertrophy in patients with hypertension and normal electrocardiogram

Background: Electrocardiography (ECG) has low sensitivity for detecting left ventricular hypertrophy (LVH), while echocardiography cannot be routinely performed. Design/methods: In this study we evaluate the prevalence of LVH and diastolic dysfunction in hypertensive patients with normal ECG. We excluded patients with cardiovascular (CV) diseases, diabetes, chronic kidney disease, or presenting ECG-LVH or other ECG anomalies. The enrolled 440 hypertensive patients underwent echocardiographic examination (Acuson Sequoia 512); LV mass was indexed by body surface area (LVMI) and LVH was defined as LVMI >125 g/m2 in men and >110 g/m2 in women. Diastolic function was evaluated by mitral inflow and tissue Doppler imaging (TDI). Results: The prevalence of LVH was 8.18% (95% confidence interval [CI] 5.97–11.1%). Multiple regression analysis showed that the only variable independently associated with LVH was duration of hypertension (p<0.001). The receiver operating characteristic (ROC) curve showed that duration of hypertension was a powerful predictor of LVH, with an area under the curve (AUC) of 0.878 and p<0.0001. Further, in patients with LVH the mean difference of LVMI from the cut-off value for LVH was 12.3 9.19 g/m2. Diastolic dysfunction, defined as early diastolic myocardial velocity (Em) <0.08 m/s, was detected only in 3.2% of patients. Conclusions: The prevalence of LVH among hypertensive patients with normal ECG, free of diabetes and of CV diseases is low; moreover, patients with echocardiographic LVH presented LVMI values that identified mild LVH. Few cases of impaired diastolic function were registered. We suggest that in hypertensive patients with such characteristics the echocardiographic examination should be reserved to those who present with higher duration of hypertension

FDI inflows and economic growth: A novel application of dose-response functions

© 2024 The Authors. Published by Macrothink Institute. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.5296/rae.v16i1.21607In this work we estimate different dose-response functions linking FDI inflows received by developing countries with their economic growth. Although the impact of FDI on the economic growth of host countries has been widely investigated in literature, findings have been ambiguous. Our study proposes a novel ‘dose-response’ approach which allows the response of recipients to different amounts of treatment in terms of FDI inflow to be observed. Our findings show that the estimated dose-response functions are statistically significant for treatment values greater than 20%, after the treatment has been rescaled to a percentage measure of the maximum dose observed, and increasing at a decreasing rate, therefore suggesting three relevant results: a) a country receiving a greater amount of FDI inflows will present a higher economic growth; b) there might be a minimum amount of FDI inflows required to reach some policy effectiveness; c) the initial amounts of FDI inflow are more effective than the subsequent ones. Results will help policymakers to better isolate the effect of FDI on economic growth and conduct informed FDI cost-benefit analysis.Published onlin

Two cases of monomicrobial intraabdominal abscesses due to KPC - 3 Klebsiella pneumoniae ST258 clone

<p>Abstract</p> <p>Background</p> <p>Knowledge of the etiology of pyogenic liver and pancreatic abscesses is an important factor in determining the success of combined surgical and antibiotic treatment. Literature shows geographical variations in the prevalence and distribution of causative organisms, and the spread of <it>Klebsiella pneumoniae </it>carbapenemase-producing bacteria is an emerging cause of abdominal infections.</p> <p>Case presentation</p> <p>We herein describe two cases of intra-abdominal abscesses due to monomicrobial infection by <it>Klebsiella pneumoniae </it>Sequence Type 258 producing <it>K. pneumoniae </it>carbapenemase 3 (KPC-Kp). In case 1, a 50-year-old HIV-negative Italian woman with chronic pancreatitis showed infection of a pancreatic pseudocystic lesion caused by KPC-Kp. In case 2, a 64-year-old HIV- negative Italian woman with pancreatic neoplasm and liver metastases developed a liver abscess due to KPC after surgery. Both women were admitted to our hospital but to different surgical units. The clonal relationship between the two isolates was investigated by pulsed-field gel electrophoresis (PFGE). In case 2, the patient was already colonized at admission and inter-hospital transmission of the pathogen was presumed. A long-term combination regimen of colistin with tigecycline and percutaneous drainage resulted in full recovery and clearance of the multidrug-resistant (MDR) pathogen.</p> <p>Conclusions</p> <p>Timely microbiological diagnosis, the combined use of new and old antibiotics and radiological intervention appeared to be valuable in managing these serious conditions. The emergence and dissemination of MDR organisms is posing an increasing challenge for physicians to develop new therapeutic strategies and control and prevention frameworks.</p

I percorsi di mentalizzazione in un intervento domiciliare con un bambino con disturbo autistico

A partire dai contributi psicodinamici che hanno proposto di considerare il Disturbo Autistico all’interno di una prospettiva relazionale, l’inquadramento teorico dell’autismo è stato arricchito dai dati di ricerca delle neuroscienze, e in particolare dalla teoria della mente e dall’individuazione dei neuroni specchio. Obiettivo: Gli autori propongono un progetto integrato che, oltre alla presa in carico psicoterapeutica, utilizza lo strumento dell’intervento domiciliare come ausilio terapeutico nei casi di autismo. In questo modo, attraverso l’intervento domiciliare, si realizzano il coinvolgimento delle diverse agenzie educative e di cura e il contenimento delle risposte affettive dei genitori. Metodologia: Attraverso la presentazione di un caso clinico vengono descritti gli obiettivi e gli strumenti dell’intervento domiciliare, sottolineando in particolare l’utilizzo dell’osservazione delle relazioni familiari, il ruolo dell’emozione nei processi di sviluppo, l’alleanza con i genitori, il lavoro di rete, la definizione del setting, il sostegno dei processi di mentalizzazione e il ricorso alla supervisione. Discussione critica e conclusioni: Dopo tre anni di intervento il mondo interno di A. è cambiato, gli oggetti interni sono divenuti meno persecutori, e nei processi mentali si è assistito a un incremento del registro simbolico, accompagnato da un utilizzo più coerente della comunicazione verbale e da una regressione delle stereotipie, cui è corrisposta una migliore qualità delle relazioni. Il materiale clinico sembra supportare l’ipotesi che lo sviluppo della capacità di mentalizzazione possa essere sostenuto dal generare e condividere emozioni

Episodic Ataxia Type 1 Mutation F184C Alters Zn2+-Induced Modulation of the Human K+ Channel Kv1.4-Kv1.1/Kvb1.1

Episodic ataxia type 1 (EA1) is a Shaker-like channelopathy characterized by continuous myokymia and attacks of imbalance with jerking movements of the head, arms, and legs. Although altered expression and gating properties of Kv1.1 channels underlie EA1, several disease-causing mechanisms remain poorly understood. It is likely that Kv1.1, Kv1.4, and Kv1.1 subunits form heteromeric channels at hippocampal mossy fiber boutons from which Zn2+ ions are released into the synaptic cleft in a Ca2+- dependent fashion. The sensitivity of this macromolecular channel complex to Zn2+ is unknown. Here, we show that this heteromeric channel possesses a high-affinity (<10 M) and a low-affinity (<0.5 mM) site for Zn2+, which are likely to regulate channel availability at distinct presynaptic membranes. Furthermore, the EA1 mutation F184C, located within the S1 segment of the Kv1.1 subunit, markedly decreased the equilibrium dissociation constants for Zn2+ binding to the high- and low-affinity sites. The functional characterization of the Zn2+ effects on heteromeric channels harboring the F184C mutation also showed that this ion significantly 1) slowed the activation rate of the channel, 2) increased the time to reach peak current amplitude, 3) decreased the rate and amount of current undergoing N-type inactivation, and 4) slowed the repriming of the channel compared with wild-type channels. These results demonstrate that the EA1 mutation F184C will not only sensitize the homomeric Kv1.1 channel to extracellular Zn2+, but it will also endow heteromeric channels with a higher sensitivity to this metal ion. During the vesicular release of Zn2+, its effects will be in addition to the intrinsic gating defects caused by the mutation, which is likely to exacerbate the symptoms by impairing the integration and transmission of signals within specific brain areas

The rationality of rainy day savers: objective and subjective determinants of individual savings in Britain

Using the largest and richest data on savings in Great Britain, six waves of the Wealth and Assets Survey from the Office for National Statistics, we compare standard life cycle models of saving with models using more ‘subjective’ measures, and the added dimension of longitudinal data. Whilst the life cycle model provides a benchmark, regular criticisms remain, particularly people’s propensity to continue saving at older ages. Data on attitudes attenuate that issue, and panel data largely eliminate it. Our results confirm empirically, for Great Britain, the importance of some of the objective determinants of savings included in life cycle theory. When we look at more subjective ones, we show that other factors, including self-rated health and financial pressure, provide an enhanced direct explanation of the propensity to save. Individuals who regard themselves as ‘rainy day savers’ tended to save more, irrespective of their demographic or financial circumstances. Results are robust to different specifications