Miracle-dz/UniFAR-FTUs huggingface dataset:
Information content of protein sequences.

The complexity of large sets of non-redundant protein sequences is measured. This is done by estimating the Shannon entropy as well as applying compression algorithms to estimate the algorithmic complexity. The estimators are also applied to randomly generated surrogates of the protein data. Our results show that proteins are fairly close to random sequences. The entropy reduction due to correlations is only about 1%. However, precise estimations of the entropy of the source are not possible due to finite sample effects. Compression algorithms also indicate that the redundancy is in the order of 1%. These results confirm the idea that protein sequences can be regarded as slightly edited random strings. We discuss secondary structure and low-complexity regions as causes of the redundancy observed. The findings are related to numerical and biochemical experiments with random polypeptides.
Application of a circulating-cathodic-antigen (CCA) strip test and real-time PCR, in comparison with microscopy, for the detection of Schistosoma haematobium in urine samples from Ghana

Abstract In the detection of parasitic infection, the traditional methods based on microscopy often have low sensitivity and/or specificity compared with the newer, molecular tests. An assay based on real-time PCR and a reagent strip test for detecting circulating cathodic antigen (CCA) have both now been compared with urine filtration and microscopy, in the detection of Schistosoma haematobium infections. Urine samples, obtained from 74 'cases' in areas of Ghana with endemic S. haematobium and 79 'controls' from non-endemic areas, were each checked using the three methods. With the results of the filtration and microscopy taken as the 'gold standard', real-time PCR was found to be 100% specific and 89% sensitive whereas the CCA strips were 91% specific and 41% sensitive. With the samples found to contain ≥50 eggs/10 ml (indicating relatively intense infections), the sensitivities of the PCR and CCA were higher, at 100% and 62%, respectively. As expected, egg counts were negatively correlated with the number of amplification cycles needed, in the PCR, to give a signal that exceeded the background (r=−0.38; P<0.01). Although the real-time PCR and CCA strip tests are very different, both show promise in the detection of S. haematobium infections. The PCR has optimal specificity and high sensitivity but the specificity of the CCA strips and the sensitivity of both tools could still be improved. A more thorough re-evaluation of the sensitivity and specificity of microscopy and these newer diagnostic methods, with an estimation of the cost-effectiveness of each technique, is recommended.
Prevalence of Atherosclerotic Plaque in Young and Middle-Aged Asymptomatic Individuals: The Bogalusa Heart Study

Objectives To determine the prevalence of carotid and femoral artery atherosclerotic plaque in a community-based population of asymptomatic African American and white men and women, with an age range of 29 to 51 years, and the potential relations with cardiovascular risk factors. Methods Between 2007 and 2010, 914 subjects, 58% women and 69% white, who were part of the Bogalusa Heart Study, an ongoing study of a southern biracial community in Bogalusa, Louisiana, were followed up from childhood through adulthood and assessed for plaque formation using ultrasound. Of the total number of subjects, those with a history of cardiovascular/cerebrovascular events were excluded. Results Plaque prevalence ranged from 8% to 14%, with greater frequency in white men. Plaque formation was also associated with smoking, hypertension, diabetes mellitus, age, and white race, in descending order. Conclusions In this population, studied sequentially since 1973, the presence of plaque correlated with widely recognized cardiovascular risk factors, although we did not detect significant contributions from either obesity or elevated lipids, including low-density lipoprotein cholesterol. It is possible that interventions, such as diet alteration and statin therapy, may have a positive impact on these potential contributors to plaque formation, and hypertension, diabetes mellitus and smoking remain of great importance.
Molecular imaging of prostate cancer

Purpose of review Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Recent findings Several PET tracers are active in early-stage and late-stage prostate cancer in humans. F18-Fluorodeoxyglucose (FDG), C11/F18-choline and sodium F18-fluoride have been studied most extensively. There is a growing body of literature supporting the utility of choline in early-stage prostate cancer. FDG and sodium F18-fluoride are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-fluorodihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel androgen receptor-targeted therapies. Prostate-specific membrane antigen PET tracers are in the early stages of clinical development. Summary Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer.
Degradation of p53, Not Telomerase Activation, by E6 Is Required for Bypass of Crisis and Immortalization by Human Papillomavirus Type 16 E6/E7

ABSTRACT Bypass of two arrest points is essential in the process of cellular immortalization, one of the components of the transformation process. Expression of human papillomavirus type 16 E6 and E7 together can escape both senescence and crisis, processes which normally limit the proliferative capacity of primary human keratinocytes. Crisis is thought to be mediated by telomere shortening. Because E6 stimulates telomerase activity and exogenous expression of the TERT gene with E7 can immortalize keratinocytes, this function is thought to be important for E6 to cooperate with E7 to bypass crisis. However, it has also been reported that E6 dissociates increased telomerase activity from maintenance of telomere length and that a dominant-negative p53 molecule can substitute for E6 in cooperative immortalization of keratinocytes with E7. Thus, to determine which functions of E6 are required to allow bypass of crisis and immortalization of keratinocytes with E7, immortalization assays were performed using specific mutants of E6, in tandem with E7. In these experiments, every clone expressing an E6 mutant capable of degrading p53 was able to bypass crisis and immortalize, regardless of telomerase induction. All clones containing E6 mutants incapable of degrading p53 died at crisis. These results suggest that the ability of E6 to induce degradation of p53 compensates for continued telomere shortening in E6/E7 cells and demonstrate that degradation of p53 is required for immortalization by E6/E7, while increased telomerase activity is dispensable.
Temporal overlap of excitatory and inhibitory afferent input in guinea‐pig CA1 pyramidal cells

1 The temporal interaction of evoked synaptic excitation and GABAA‐mediated inhibition was examined in CA1 pyramidal cells. Single and paired intracellular recordings were carried out in pyramidal cell dendrites and somata, and interneurons of the guinea‐pig hippocampal slice. Current‐clamp, sharp electrode and whole‐cell voltage‐clamp recordings were made. 2 Kinetics of dendritic and somatic inhibitory responses were similar. Notably, kinetics of dendritic unitary IPSPs were as fast as kinetics of somatic unitary IPSPs. 3 GABAA‐mediated influences were present throughout the orthodromic pyramidal cell EPSP/EPSC. Comparison of the kinetics of pharmacologically isolated monosynaptic IPSPs, IPSCs and inhibitory conductances (gGABAA), showed fastest kinetics for gGABAA. Close temporal overlap was observed between monosynaptic gGABAA and the rising phase of the evoked EPSP/EPSC. The onset of gGABAA coincided with or preceded onset of the EPSP/EPSC. 4 Onsets of feedforward IPSPs coincided with the rising phase of the pyramidal cell EPSP in > 80 % of paired recordings. Fastest feedforward inhibitory responses exerted near complete overlap with evoked excitation. 5 Onsets of recurrent IPSPs did not occur during the rising phase of the evoked EPSP, but > 3·0 ms after the peak of the pyramidal cell EPSP. 6 Orthodromically evoked interneuron spikes were observed at stimulation intensities that were below the threshold for eliciting EPSPs in concomitantly recorded pyramidal cells. The activation of feedforward inhibitory responses by weakest excitatory input, and the large temporal overlap between feedforward inhibition and evoked excitation, suggest that in situ any excitatory input in CA1 is effectively controlled by fast synaptic inhibition.
Effect of resistance training on neuromuscular junctions of young and aged muscles featuring different recruitment patterns

To examine the effects of aging on neuromuscular adaptations to resistance training (i.e., weight lifting), young (9 months of age) and aged (20 months of age) male rats either participated in a 7‐week ladder climbing protocol with additional weight attached to their tails or served as controls (n = 10/group). At the conclusion, rats were euthanized and hindlimb muscles were quickly removed and frozen for later analysis. Longitudinal sections of the soleus and plantaris muscles were collected, and pre‐ and postsynaptic features of neuromuscular junctions (NMJs) were visualized with immunofluorescence staining procedures. Cross‐sections of the same muscles were histochemically stained to determine myofiber profiles (fiber type and size). Statistical analysis was by two‐way ANOVA (main effects of age and treatment) with significance set at P ≤ 0.05. Results revealed that training‐induced remodeling of NMJs was evident only at the postsynaptic endplate region of soleus fast‐twitch myofibers. In contrast, aging was associated with pre‐ and postsynaptic remodeling in fast‐ and slow‐twitch myofibers of the plantaris. Although both the soleus and the plantaris muscles failed to display either training or aging‐related alterations in myofiber size, aged plantaris muscles exhibited an increased expression of type I (slow‐twitch) myofibers in conjunction with a reduced percentage of type II (fast‐twitch) myofibers, suggesting early stages of sarcopenia. These data demonstrate the high degree of specificity of synaptic modifications made in response to exercise and aging and that the sparsely recruited plantaris is more vulnerable to the effects of aging than the more frequently recruited soleus muscle. © 2014 Wiley Periodicals, Inc.
Intermittent Stimulation Delays Adaptation to Electrocutaneous Sensory Feedback

Electrotactile displays deliver information to the user by means of electrocutaneous stimulation. If such displays are used in prostheses, the functionality depends on long term stability of this information channel. The perceived sensation, however, decays within 15 min due to central adaptation if the stimulation is applied continuously and at constant strength. In this study, the effects of stimulus amplitude and intermittent stimulation on adaptation were investigated in ten healthy subjects. The perceived sensation was recorded during 15 min of constant stimulation using a visual analog scale (VAS). The sensation level with time thus measured were parameterized by the initial sensation level, the time constant of decay and the end sensation level after fitting of an exponential function through the VAS data. The time constant increased significantly when applying a high stimulation level (at 80% of the range between sensation and pain thresholds) if compared with lower levels of stimulation (20% and 50%) during continuous stimulation. Intermittent stimulation at this high stimulation level significantly increased end sensation level.
Retinoic acid-induced IgG production in TLR-activated human primary B cells involves ULK1-mediated autophagy

In the present study we have established a vital role of autophagy in retinoic acid (RA)-induced differentiation of toll-like receptor (TLR)-stimulated human B cells into Ig-secreting cells. Thus, RA enhanced autophagy in TLR9- and CD180-stimulated peripheral blood B cells, as revealed by increased levels of the autophagosomal marker LC3B-II, enhanced colocalization between LC3B and the lysosomal marker Lyso-ID, by a larger percentage of cells with more than 5 characteristic LC3B puncta, and by the concomitant reduction in the level of SQSTM1/p62. Furthermore, RA induced expression of the autophagy-inducing protein ULK1 at the transcriptional level, in a process that required the retinoic acid receptor RAR. By inhibiting autophagy with specific inhibitors or by knocking down ULK1 by siRNA, the RA-stimulated IgG production in TLR9- and CD180-mediated cells was markedly reduced. We propose that the identified prominent role of autophagy in RA-mediated IgG-production in normal human B cells provides a novel mechanism whereby vitamin A exerts its important functions in the immune system.
A Fast Hopping Frequency Synthesizer for UWB Systems in a CMOS Technology

A 3 to 5 GHz fast hopping frequency synthesizer for multi-band OFDM UWB applications is designed using a 0.18 mum CMOS technology. The frequency synthesizer operates in the mode 1 bands (centered at 3432 MHz, 3960 MHz, and 4488 MHz). Single-sideband mixer up-converts or down-converts the 528 MHz quadrature signals of ring VCO mixing 3960 MHz LC VCO signals. The sideband suppression is less than -32 dBc for 3432 MHz and -26 dBc for 4488 MHz and band switching time from 4488 MHz to 3432 MHz is measured about 2 ns. Phase noise of the LC VCO and the ring VCO is about -110 dBc/Hz and -98 dBc/Hz at 1 MHz offset frequency, respectively. The total power consumption of the proposed frequency synthesizer is about 68 mW with a 1.8 V supply voltage
Physical activity level is not a determinant of autonomic nervous system activity and clinical severity in children/adolescents with sickle cell anemia: A pilot study

Autonomic nervous system (ANS) activity has been suggested to modulate the clinical severity of sickle cell anemia (SCA) by increasing the risk for vaso‐occlusive events. Regular physical activity (PA) is known to improve ANS activity and health status in several cardiovascular and metabolic diseases. Whether regular PA improves the health status of SCA patients remains unknown.
A Chloride Ion Channel in Halocynthia roretzi Hemocytes is Associated with PO Activity but Not Pigmentation During the Contact Reaction

Abstract When hemocytes of two different individuals of the solitary ascidian Halocynthia roretzi come into contact (allogeneic recognition), they devacuolate in several seconds following contact, release phenoloxidase (PO) into the supernatant, and form coagulates. These coagulates show brown pigmentation. This reaction is referred to as the contact reaction (CR). In this study, the CR-inhibitory monoclonal antibody ku-4-96, which inhibits devacuolation, increase in PO activity, coagulation, and pigmentation, was constructed. This antibody is thought to exert its inhibitory action at an early stage in the CR. A differential display analysis was conducted by using ku-4-96 to search exhaustively for differentially expressed genes involved in the CR. One of the genes cloned was downregulated in the presence of ku-4-96 and upregulated during the CR. This gene showed very high similarity to the Cl– channel gene ClC-2 and was named HrClC-2. We examined the effects of Cl– channel inhibitors on the CR to examine whether the Cl– channel was involved in the CR signal cascade. Devacuolation, coagulation, and pigmentation were not affected by different concentrations of these inhibitors, which inhibited PO activity. This suggests that the PO activity is independent of these other phenomena occurring during the CR.
Initiation factor 2 crystal structure reveals a different domain organization from eukaryotic initiation factor 5B and mechanism among translational GTPases

Significance Initiation factor 2 (IF2) is a GTPase that functions within the 30S ribosomal initiation complex and promotes its joining with the 50S ribosomal subunit to form a 70S ribosome. The role of IF2 in translation initiation is not well understood. We present an atomic resolution crystal structure of the full-length IF2, and we are able to explain why prokaryotes and eukaryotes have similar proteins with different mechanisms to guide ribosome assembly. We provide a structural explanation for why the mechanism of IF2 is unique among translational GTPases and acts more as a novel conformational switch. The initiation of protein synthesis uses initiation factor 2 (IF2) in prokaryotes and a related protein named eukaryotic initiation factor 5B (eIF5B) in eukaryotes. IF2 is a GTPase that positions the initiator tRNA on the 30S ribosomal initiation complex and stimulates its assembly to the 50S ribosomal subunit to make the 70S ribosome. The 3.1-Å resolution X-ray crystal structures of the full-length Thermus thermophilus apo IF2 and its complex with GDP presented here exhibit two different conformations (all of its domains except C2 domain are visible). Unlike all other translational GTPases, IF2 does not have an effecter domain that stably contacts the switch II region of the GTPase domain. The domain organization of IF2 is inconsistent with the “articulated lever” mechanism of communication between the GTPase and initiator tRNA binding domains that has been proposed for eIF5B. Previous cryo-electron microscopy reconstructions, NMR experiments, and this structure show that IF2 transitions from being flexible in solution to an extended conformation when interacting with ribosomal complexes.
Four weeks of running sprint interval training improves cardiorespiratory fitness in young and middle-aged adults

ABSTRACT The purpose of this study was to determine the effectiveness of a 4-week running sprint interval training protocol to improve both aerobic and anaerobic fitness in middle-aged adults (40–50 years) as well as compare the adaptations to younger adults (20–30 years). Twenty-eight inactive participants – 14 young 20–30-year-olds (n = 7 males) and 14 middle-aged 40–50-year-olds (n = 5 males) – completed 4 weeks of running sprint interval training (4 to 6, 30-s “all-out” sprints on a curved, self-propelled treadmill separated by 4 min active recovery performed 3 times per week). Before and after training, all participants were assessed for maximal oxygen consumption (VO2max), 2000 m time trial performance, and anaerobic performance on a single 30-s sprint. There were no interactions between group and time for any tested variable, although training improved relative VO2max (young = 3.9, middle-aged = 5.2%; P < 0.04), time trial performance (young = 5.9, middle-aged = 8.2%; P < 0.001), peak sprint speed (young = 9.3, middle-aged = 2.2%; P < 0.001), and average sprint speed (young = 6.8, middle-aged = 11.6%; P < 0.001) in both young and middle-aged groups from pre- to post-training on the 30-s sprint test. The current study demonstrates that a 4-week running sprint interval training programme is equally effective at improving aerobic and anaerobic fitness in younger and middle-aged adults.
Should Y stay or should Y go: The evolution of non‐recombining sex chromosomes

Gradual degradation seems inevitable for non‐recombining sex chromosomes. This has been supported by the observation of degenerated non‐recombining sex chromosomes in a variety of species. The human Y chromosome has also degenerated significantly during its evolution, and theories have been advanced that the Y chromosome could disappear within the next ∼5 million years, if the degeneration rate it has experienced continues. However, recent studies suggest that this is unlikely. Conservative evolutionary forces such as strong purifying selection and intrachromosomal repair through gene conversion balance the degeneration tendency of the Y chromosome and maintain its integrity after an initial period of faster degeneration. We discuss the evidence both for and against the extinction of the Y chromosome. We also discuss potential insights gained on the evolution of sex‐determining chromosomes by studying simpler sex‐determining chromosomal regions of unicellular and multicellular microorganisms.
Day‐Night Variations of Serum Interleukin‐6 in Patients with Severe Obstructive Sleep Apnea Syndrome before and after Continuous Positive Airway Pressure (CPAP)

Obstructive sleep apnea syndrome (OSAS) causes intermittent hypoxia and increases in sympathetic activity and contributes to cardiovascular disorders. Interleukin‐6 (IL‐6) is one of the important proinflammatory cytokines. We examined the levels of serum IL‐6 concentrations in nine patients with severe OSAS at four different clock times during the 24 h before and after three months of continuous positive airway pressure (CPAP) therapy. Serum IL‐6 levels were significantly reduced after CPAP therapy by 46% (6.2±1.0 vs. 3.3±0.4 pg/ml, p<0.005). No significant 24 h variation of serum IL‐6 in severe OSAS patients was found before CPAP; however, a significant 24 h variation of serum IL‐6 was found after CPAP. Intermittent hypoxia during sleep may contribute to systemic inflammation and result in an elevation of serum IL‐6 in severe OSAS patients.
Novel digital microfluidic system using a surface acoustic wave device

A droplet manipulation is one application of a surface acoustic wave (SAW) device. In this paper, a novel digital microfluidic system using SAW device is described. The system which is called micro-laboratory consists of sensor plate/matching layer/ piezoelectric substrate. The piezoelectric substrate is used for generating the SAW. At the piezoelectric substrate and matching layer interface, the SAW radiates a longitudinal wave into the layer. When the longitudinal wave reflects at the sensor plate and matching layer interface, a bulk acoustic wave (BAW) is generated into the plate. The BAW is used to manipulate a droplet on the sensor plate. For detecting droplet characteristics, an interdigital electrode (IDE) is fabricated on the sensor plate. Using the IDE, impedance change due to a urease catalytic reaction is measured. The results indicate that the proposed system is able to use a detector of urea concentration.