Combining frequency and time domain approaches to systems with multiple spike train input and output

A frequency domain approach and a time domain approach have been combined in an investigation of the behaviour of the primary and secondary endings of an isolated muscle spindle in response to the activity of two static fusimotor axons when the parent muscle is held at a fixed length and when it is subjected to random length changes. The frequency domain analysis has an associated error process which provides a measure of how well the input processes can be used to predict the output processes and is also used to specify how the interactions between the recorded processes contribute to this error. Without assuming stationarity of the input, the time domain approach uses a sequence of probability models of increasing complexity in which the number of input processes to the model is progressively increased. This feature of the time domain approach was used to identify a preferred direction of interaction between the processes underlying the generation of the activity of the primary and secondary endings. In the presence of fusimotor activity and dynamic length changes imposed on the muscle, it was shown that the activity of the primary and secondary endings carried different information about the effects of the inputs imposed on the muscle spindle. The results presented in this work emphasise that the analysis of the behaviour of complex systems benefits from a combination of frequency and time domain methods

Direct current stimulation modulates the excitability of the sensory and motor fibres in the human posterior tibial nerve, with a long-lasting effect on the H-reflex

Several studies demonstrated that transcutaneous direct current stimulation (DCS) may modulate central nervous system excitability. However, much less is known about how DC affects peripheral nerve fibres. We investigated the action of DCS on motor and sensory fibres of the human posterior tibial nerve, with supplementary analysis in acute experiments on rats. In forty human subjects, electric pulses at the popliteal fossa were used to elicit either M-waves or H-reflexes in the Soleus, before (15 min), during (10 min) and after (30 min) DCS. Cathodal or anodal current (2 mA) was applied to the same nerve. Cathodal DCS significantly increased the H-reflex amplitude; the post-polarization effect lasted up to ~ 25 min after the termination of DCS. Anodal DCS instead significantly decreased the reflex amplitude for up to ~ 5 min after DCS end. DCS effects on M-wave showed the same polarity dependence but with considerably shorter after-effects, which never exceeded 5 min. DCS changed the excitability of both motor and sensory fibres. These effects and especially the long-lasting modulation of the H-reflex suggest a possible rehabilitative application of DCS that could be applied either to compensate an altered peripheral excitability or to modulate the afferent transmission to spinal and supraspinal structures. In animal experiments, DCS was applied, under anaesthesia, to either the exposed peroneus nerve or its Dorsal Root, and its effects closely resembled those found in human subjects. They validate therefore the use of the animal models for future investigations on the DCS mechanisms

Molecular biology for the radiation oncologist: The 5rs of radiobiology meet the hallmarks of cancer

ABSTRACT: Recent advances in our understanding of the biology of cancer have provided enormous opportunities for the development of novel therapies against specific molecular targets. It is likely that most of these targeted therapies will have only modest single agent activities but may have the potential to accentuate the therapeutic effects of ionising radiation. In this introductory review, the 5Rs of classical radiobiology are interpreted in terms of their relationship to the hallmarks of cancer. Future articles will focus on the specific hallmarks of cancer and will highlight the opportunities that exist for designing new combination treatment regimens. Harrington, K. et al. (2007). Clinical Oncology 19, 561e57

Total Sitting Time and Sitting Pattern in Postmenopausal Women Differ by Hispanic Ethnicity and are Associated With Cardiometabolic Risk Biomarkers.

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P<0.001) and had shorter (3.6 minutes less, P=0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women (P-interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted

Men With a Terminal Illness Relax Their Criteria for Facial Attractiveness

According to the life history paradigm, in life-threatening conditions, sexual selection criteria are relaxed in order to increase the probability of a last resort reproduction, ultimately contributing to reproductive success. This should be reflected in loosened mating preferences — a process observed in nonhuman animals. Studies investigating this aspect in humans, however, are scarce. This study explored the aesthetic preferences towards facial and nonfacial stimuli in terminally ill patients with heart failure (HF) and their healthy, same-sex peers. The aim was to examine if these two groups of men demonstrate different patterns of aesthetic judgments. Using a 7-point scale, 65 male patients with HF and 143 healthy men evaluated the perceived attractiveness of 15 photographs (five adult male faces, five adult female faces, and five nonfacial pictures). A mixed-design analysis of variance was run to assess group differences in aesthetic preferences. Compared to healthy controls, stimuli. HF patients rated the pictures using significantly higher scores, but this applied only to male and female, but not nonfacial, stimuli. We propose that lower criteria for facial attractiveness in HF patients are linked to relaxation of mate preferences as a result of a life-threatening conditions, and that this process can be an adaptive mating strategy from an ultimate, evolutionary perspective. However, other mechanisms (e.g., seeking social support) may be also responsible for the observed patterns

Regulation of human chorionic gonadotropin beta subunit expression in ovarian cancer

Expression of human chorionic gonadotropin beta subunit by cancers is extensively documented, yet regulation of the multiple genes that can code for this protein is poorly understood. The aim of the study was to examine the mechanisms regulating CGB gene expression in ovarian cancer. Expression of CGB genes and SP1, SP3, TFAP2A transcription factor genes was evaluated by RT-qPCR. The methylation status of CGB genes promoter regions was examined by methylation-specific PCR. mRNA arising from multiple CGB genes was detected in both ovarian control and malignant tissues. However, expression of CGB3-9 genes was shown to be significantly higher in malignant than healthy ovarian tissues. CGB1 and CGB2 transcripts were shown to be present in 20% of ovarian cancers, but were not detected in any of the control samples. Malignant tissues were characterized by DNA demethylation of CGB promoter regions. In ovarian cancer CGB expression positively correlated with TFAP2A transcripts level and expression of TFAP2A transcription factor was significantly higher in cancer than in control tissues. In contrast SP3 expression level was significantly lower in ovarian tumours than in control ovarian tissue. In ovarian cancers increased expression of human chorionic gonadotropin beta subunit is associated with demethylation of CGB promoter regions. CGB3-9 expression level strongly correlates with expression of the TFAP2A transcription factor. Presence of mRNA arising from CGB1 and CGB2 genes appears to be a unique feature of a subset of ovarian cancers

EVALUATION OF MODERN HERITAGE ASSETS IN POZNAN USING MONOTONIC DECISION RULES

The protection of cultural heritage is an important task of communities on various levels of social organization. The institutionalization of the processes of protection of modern heritage assets provides the necessary instruments (legislative, juridical, financial) enabling the actual realization of the assumed tasks. The criterion of age, which is still a dominating premise for monument protection, proved not to be sufficient, especially concerning protection of monuments of Modernism. A step that led to the determination of the value of individual architectural objects of the 20th century was the establishment of 10 evaluation criteria proposed by historians of architecture in Warsaw, and afterwards in Poznan.In this work, we focus on the architectural value of post-war buildings, which are most difficult to evaluate. Furthermore, we wanted to apply AI to objectify the process of decision making. The adequacy of the Dominance-based Rough Set Approach (DRSA) method has been established. This method takes into account preference orders on criteria and models patterns observed in data in terms of monotonic “if &hellip;, then &hellip;” decision rules.</p

Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation.

The chemical modification of tRNA bases by sulfur is crucial to tune translation and to optimize protein synthesis. In eukaryotes, the ubiquitin-related modifier 1 (Urm1) pathway is responsible for the synthesis of 2-thiolated wobble uridine (U34 ). During the key step of the modification cascade, the E1-like activating enzyme ubiquitin-like protein activator 4 (Uba4) first adenylates and thiocarboxylates the C-terminus of its substrate Urm1. Subsequently, activated thiocarboxylated Urm1 (Urm1-COSH) can serve as a sulfur donor for specific tRNA thiolases or participate in ubiquitin-like conjugation reactions. Structural and mechanistic details of Uba4 and Urm1 have remained elusive but are key to understand the evolutionary branch point between ubiquitin-like proteins (UBL) and sulfur-relay systems. Here, we report the crystal structures of full-length Uba4 and its heterodimeric complex with its substrate Urm1. We show how the two domains of Uba4 orchestrate recognition, binding, and thiocarboxylation of the C-terminus of Urm1. Finally, we uncover how the catalytic domains of Uba4 communicate efficiently during the reaction cycle and identify a mechanism that enables Uba4 to protect itself against self-conjugation with its own product, namely activated Urm1-COSH

Hypercapnic Chemosensitivity in Patients with Heart Failure: Relation to Shifts in Type-1 Insulin-Like Growth Factor and Sex Hormone-Binding Globulin Levels

In patients suffering from heart failure (HF), autonomic imbalance develops even at early stages along with derangements of cardiopulmonary reflex control and abnormalities in metabolism of several hormones. In 34 men with stable systolic HF, we investigated hypercapnic chemosensitivity (HCS, liter/min·mm Hg) measured using the rebreathing method and defined as the slope of the regression line relating minute ventilation (VE, liter/min) to end­tidal carbon dioxide concentration (PETCO₂ , mm Hg). Serum levels of testosterone, dehydroepiandrosterone sulfate, type­1 insulin­like growth factor (IGF­1), sex hormonebinding globulin (SHBG), estradiol, and cortisol were measured using immunoassays. We found that there were no associations between HCS and clinical variables, applied therapy, and co­morbidities (all P > 0.2). Augmented HCS was accompanied by increased serum SHBG (when expressed in nM, r = 0.43, P < 0.05; when expressed as percentage of the agematched reference values, r = 0.62, P < 0.001) and the reduced serum IGF­1 (when expressed in ng/ml and as percentage of the above­mentioned values, r = –0.49, P < 0.05, and r = = –0.47, P = 0.007, respectively). The HCS was not related to serum levels of all the remaining analyzed hormones (all P > 0.2). Thus, it may be suggested that the hormone stimuli can noticeably modify the reflex mechanisms in cardiorespiratory control in the clinical setting of cardiovascular pathology.У пацієнтів із серцевою недостатністю (СН) навіть на ранніх стадіях захворювання розвивається автономний дисбаланс паралельно з розладами контролю серцево­судинної системи та відхиленнями метаболізму деяких гормонів від норми. Ми досліджували хемочутливість до гіперкапнії (HCS) у 34 чоловіків із СН, використовуючи метод зворотного дихання. Така чутливість визначалась як нахил лінії регресії при співставленні хвилинного об’єму вентиляції (л/хв) та кінцевої концентрації двооксиду вуглецю (мм рт. ст.). Рівні тестостерону, дигідроепіандростерону сульфату, інсулінподібного фактора росту типу 1 (IGF­1), глобуліну, що зв’язує статеві гормони (SHBG), естрадіолу та кортизолу визначали в сироватці крові, використовуючи імунологічні методики. Як виявилося, зв’язки між рівнем HCS, з одного боку, та клінічними показниками, застосованою терапією та супутніми захворюваннями – з другого, були відсутніми (в усіх випадках P > 0.2). Підвищена HCS супроводжувалася підвищеними рівнями SHBG (для концентрацій у наномолях на 1 л r = 0.43, P < 0.05, а для нормованих значень, наведених щодо певної вікової групи, r = 0.62, P < 0.001) та низькими рівнями IGF­1 (для концентрацій у нанограмах на 1 мл та для наведених нормованих значень r = –0.49, P < 0.05 та r = –0.47, P = 0.007 відповідно). Значення HCS не виявляли будь­яких зв’язків з рівнями всіх досліджених гормонів у сироватці. Це дозволяє думати, що гормональні стимули можуть помітно модифікувати рефлекторні механізми контролю серцево­судинної системи у клінічних випадках її патологій

Presynaptic actions of 4-Aminopyridine and γ-aminobutyric acid on rat sympathetic ganglia in vitro

Responses to bath-applications of 4-aminopyridine (4-AP) and -aminobutyric acid (GABA) were recorded intracellularly from neurones in the rat isolated superior cervical ganglion. 4-aminopyridine (0.1–1.0 mmol/l) usually induced spontaneous action potentials and excitatory postsynaptic potentials (EPSPs), which were blocked by hexamethonium. Membrane potential was unchanged; spike duration was slightly increased. Vagus nerve B-and C-fibre potentials were prolonged. In 4-AP solution (0.1–0.3 mmol/l), GABA (0.1 mmol/l), 3-aminopropanesulphonic acid or muscimol evoked bursts of spikes and EPSPs in addition to a neuronal depolarization. These bursts, which were not elicited by glycine, glutamate, taurine or (±)-baclofen, were completely antagonised by hexamethonium, tetrodotoxin or bicuculline methochloride. It is concluded that: (a) 4-AP has a potent presynaptic action on sympathetic ganglia; (b) presynaptic actions of GABA can be recorded postsynaptically in the presence of 4-AP; and (c) the presynaptic GABA-receptors revealed in this condition are similar to those on the postsynaptic membrane