Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Comparison of Serine Protease Autotransporters of Enterobacteriaceae

ABSTRACT The plasmid-encoded toxin (Pet) of enteroaggregative Escherichia coli (EAEC) belongs to a family of high-molecular-weight serine protease autotransporters of Enterobacteriaceae (SPATEs) which also includes Pic from EAEC and Shigella flexneri, EspC from enteropathogenic E. coli, EspP from enterohemorrhagic E. coli, Sat from uropathogenic E. coli, Tsh from avian pathogenic E. coli, and SepA from S. flexneri. Phylogenetic analysis shows the SPATE proteins to represent a distinct subfamily of autotransporters with amino acid identities ranging from 35 to 55%, providing a powerful resource to direct structure-function studies. In this study, we show that these related proteins are proteases with divergent substrate specificities, suggesting different functions. The cleavage profile of oligopeptides was found to be unique for each SPATE protein. The SPATEs showed proteolytic activity for several substrates, namely mucin, pepsin, human coagulation factor V, and erythroid spectrin. The cleavage of spectrin has been hypothesized as the mechanism through which Pet induces cytopathic effects. However, whereas Pet, Sat, and EspC cleaved spectrin, only Pet and Sat elicited cytopathic effects; the remaining SPATEs did not cause any morphological changes to HEp-2 cell monolayers. EspC and Pet exhibited acid-dissociable binding to HEp-2 cells. However, Pet was more efficient at entering HEp-2 cells, suggesting a basis for the different abilities of these two proteases to damage cells. Our data suggest that, despite the homologies observed among these proteins, the SPATEs have different pathogenetic functions only partly dependent on their substrate specificities.
Bortezomib in Relapsed Multiple Myeloma – Results of a Non-Interventional Study by Office-Based Haematologists

Background: In Germany, bortezomib is approved for the therapy of relapsed multiple myeloma since 2004. The data which had led to the approval were based on strictly selected patients. However, no data had been recorded on bortezomib in routine practice. Materials and Methods: In this non-interventional study, bortezomib was studied under routine conditions by office-based haematologists. Data were obtained prospectively following a protocol approved by the responsible Ethics Committee. Treatment followed the prescribing information and was documented for a maximum of 8 cycles. Any therapeutic or diagnostic intervention was left to the discretion of the attending physician. The primary endpoints were efficacy and safety. Results: Overall remission rate was 61% in patients evaluable for efficacy. Response rates were not significantly different between patients ≤70 and >70 years of age, nor between patients with and without renal impairment. The median time to best response was 3 cycles. Serious adverse events included thrombocytopenia (grade 3: 6%; grade 4: 8%), peripheral neuropathy (grade 3: 8%), fatigue, and bone pain (grade 3: 6% each; grade 4: 2% each) and anaemia (grade 3: 4%). Conclusion: The efficacy and tolerability of bortezomib observed in daily practice are consistent with the results obtained in large-scale clinical trials.
Identifying the Evolutionary Building Blocks of the Cardiac Conduction System

The endothermic state of mammals and birds requires high heart rates to accommodate the high rates of oxygen consumption. These high heart rates are driven by very similar conduction systems consisting of an atrioventricular node that slows the electrical impulse and a His-Purkinje system that efficiently activates the ventricular chambers. While ectothermic vertebrates have similar contraction patterns, they do not possess anatomical evidence for a conduction system. This lack amongst extant ectotherms is surprising because mammals and birds evolved independently from reptile-like ancestors. Using conserved genetic markers, we found that the conduction system design of lizard (Anolis carolinensis and A. sagrei), frog (Xenopus laevis) and zebrafish (Danio rerio) adults is strikingly similar to that of embryos of mammals (mouse Mus musculus, and man) and chicken (Gallus gallus). Thus, in ectothermic adults, the slow conducting atrioventricular canal muscle is present, no fibrous insulating plane is formed, and the spongy ventricle serves the dual purpose of conduction and contraction. Optical mapping showed base-to-apex activation of the ventricles of the ectothermic animals, similar to the activation pattern of mammalian and avian embryonic ventricles and to the His-Purkinje systems of the formed hearts. Mammalian and avian ventricles uniquely develop thick compact walls and septum and, hence, form a discrete ventricular conduction system from the embryonic spongy ventricle. Our study uncovers the evolutionary building plan of heart and indicates that the building blocks of the conduction system of adult ectothermic vertebrates and embryos of endotherms are similar.
Exploring sand fly salivary proteins to design multiepitope subunit vaccine to fight against visceral leishmaniasis

Visceral leishmaniasis (VL) is caused by the parasites of Leishmania donovani complex, leads to the death of 20 000 to 40 000 people from 56 affected countries, worldwide. Till date, there is not a single available vaccine candidate to prevent the VL infection, and treatment only relies upon expensive and toxic chemotherapeutic options. Consequently, immunoinformatics approach was applied to design a multiepitope‐based subunit vaccine to enhance the humoral as well as cell‐mediated immunity. Constructed vaccine candidate was further subjected to evaluation on allergenicity and antigenicity and physiochemical parameters. Later on, disulfide engineering was performed to increase the stability of vaccine construct. Also, molecular docking and molecular dynamics simulation study were performed to check the binding affinity and stability of toll‐like receptor‐4 to vaccine construct complex. Finally, codon optimization and in silico cloning were performed to ensure the expression of proposed vaccine construct in a microbial expression system.
Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells

Significance We restored visual function to animal models of human blindness using a chemical compound that photosensitizes a mammalian ion channel. Virus-mediated expression of this light sensor in surviving retinal cells of blind mice restored light responses in vitro, reanimated innate light avoidance, and enabled learned visually guided behavior. The treatment also restored light responses to the retina of blind dogs. Patients that might benefit from this treatment would need to have intact ganglion cell and nerve fiber layers. In general, these are patients diagnosed with retinitis pigmentosa and some forms of Leber congenital amaurosis. Patients diagnosed with other types of blindness, for example, age-related macular degeneration or diabetic retinopathy, would not be candidates for this treatment. Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0460). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0460 was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0460 was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0460 in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0460 in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0460 was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.
Comparison of Consanguinity between Parents of Hearing Impaired and Public School Children with Estimation of Risk.

Deafness is the hidden disability and the most common human sensory defects which lead to poor educational and employment prospects of childhood. Is there any association of consanguinity and hearing loss or are there any difference of association of consanguinity and hearing loss in specialized and public school children and how much risk is associated? --were the research questions of this study. Total 428 participants have been selected randomly. Hearing impaired were 186 participants and 242 participants were normal hearing school boy. This was a case control, analytical, hypotheses testing study. In normal public school children group, consanguinity was present in 2.5% parents. The rest were married with non relatives. In parents of hearing impaired children group, consanguinity was very high (17.2%). Pearson chi-square test and Odds ratio analysis was done. The value was less than 0.05 and ratio was 8.173. The 'p' value of Pearson chi-square test was less than 0.05. So, the test was highly significant at 95% confidence interval. Odds ratio showed that the risk of profound sensorineural hearing loss in the baby of parents of consanguineous marriages 8.173 times higher than that of non consanguineous marriages.
Cardiac UCP2 Expression and Myocardial Oxidative Metabolism During Acute Septic Shock in the Rat

Septic shock decreases cardiac hydraulic work relative to the rate of myocardial oxygen consumption, causing decreased mechanical efficiency (hydraulic work/myocardial oxygen consumption). This study tested whether the mitochondrial uncoupling protein UCP2 was responsible for decreased cardiac mechanical efficiency after polymicrobial septic shock. Sepsis was initiated in ketamine/xylazine-anesthetized rats by cecal ligation and puncture (CLP). Steady-state mRNA content was quantified by Northern blot analysis, and protein content was estimated by western blot. Additional hearts were removed after 12 h and perfused in working mode to measure work (mmHg x mL/min/100g dry wt) and efficiency (CE= work/ oxygen consumption, %). The 72-h mortality rate was 80%, and deaths occurred between 12–32 h. Cardiac work (152 ± 15, shock vs. 235 ± 16, control;P < 0.05) and cardiac efficiency (4.0 ± 0.4 vs. 5.6 ± 0.3;P < 0.05) were significantly decreased when hearts were isolated 12 h after CLP. Myocardial UCP2 mRNA expression was increased by 52% (12 h) compared with control hearts; however, there was no detectable UCP2 protein in mitochondria isolated from either control or septic hearts. Conclusions: Although polymicrobial sepsis decreased cardiac mechanical efficiency and increased UCP-2 expression coincident with premortal hypothermia, we did not detect any evidence of UCP-2 protein in septic heart muscle. These data argue against the hypothesis that UCP-2 causes decreased cardiac mechanical efficiency in septic shock.
Adaptive-order fractional Fourier transform features for speech recognition

We propose an acoustic feature for speech recognition based on the combination of MFCC and fractional Fourier transform (FrFT). Since the transform order is critical for the performance of FrFT, we use the ambiguity function to adaptively determine the optimal orders of FrFT for each frame. The performance of the proposed feature is compared with traditional MFCCs on recognizing speech of isolated and connected digits under both clean and noisy backgrounds. The recognition results and detailed confusion matrices are given and analyzed, which implies that the proposed feature is promising in certain speech processing fields.
The gamma amino butyric acid (GABA) receptor alpha‐3 subunit gene polymorphism in unipolar depressive disorder: A genetic association study

There is evidence that genes coding for the gamma aminobutyric acid (GABA) receptor may be involved in the etiology of affective disorders. Recently, an association between a CA‐repeat in the GABRA 3 gene and bipolar disorder had been reported. The present study aimed at investigating the association between this polymorphism and unipolar major depressive disorder. The sample consisted of 201 unipolar depressive patients and 151 healthy subjects. All study participants were unrelated German individuals of the same ethnogeographical origin. No differences in genotype frequencies between unipolar patients and healthy subjects were found for GABRA 3 (P = 0.08). However, a significant difference of allelic frequencies was observed in female patients (n = 128) compared to female controls (n = 81) (P ≤ 0.0001). This effect was not present in the group of male patients (n = 73) compared to male healthy subjects (n = 70) (P = 0.24). The results of our study indicate that GABRA 3 gene might also be involved in the genetic pathophysiology of unipolar major depressive disorder (at least in female patients), even if the findings do not support a predominant role of GABRA 3. © 2003 Wiley‐Liss, Inc.
Estimates of the size of key populations at risk for HIV infection: men who have sex with men, female sex workers and injecting drug users in Nairobi, Kenya

Objectives Size estimates of populations at higher risk for HIV infection are needed to help policy makers understand the scope of the epidemic and allocate appropriate resources. Population size estimates of men who have sex with men (MSM), female sex workers (FSW) and intravenous drug users (IDU) are few or non-existent in Nairobi, Kenya. Methods We integrated three population size estimation methods into a behavioural surveillance survey among MSM, FSW and IDU in Nairobi during 2010–2011. These methods included the multiplier method, ‘Wisdom of the Crowds’ and an approach that drew on published literature. The median of the three estimates was hypothesised to be the most plausible size estimate with the other results forming the upper and lower plausible bounds. Data were shared with community representatives and stakeholders to finalise ‘best’ point estimates and plausible bounds based on the data collected in Nairobi, a priori expectations from the global literature and stakeholder input. Results We estimate there are approximately 11 042 MSM with a plausible range of 10 000–22 222, 29 494 FSW with a plausible range of 10 000–54 467 FSW and approximately 6107 IDU and plausibly 5031–10 937 IDU living in Nairobi. Conclusions We employed multiple methods and used a wide range of data sources to estimate the size of three hidden populations in Nairobi, Kenya. These estimates may be useful to advocate for and to plan, implement and evaluate HIV prevention and care programmes for MSM, FSW and IDU. Surveillance activities should consider integrating population size estimation in their protocols.
Tables and smartphones for teaching in electrical and electronics engineering

Tablets and Smartphones are becoming objects of everyday life. These devices are commonly used to reading newspapers, GPS navigator, make purchases online, check email, etc . These touch devices are also used as tools for learning, so they should take advantage of the synergy of both students usage as teachers are accustomed to using. Enter applications on these devices get the student is next to the content and always wear accessible 24 hours a day is one of the objectives to be achieved. Applications that can be installed on these devices allow dynamic learning objects and interactive exercises that allow learning autocorrections more fluid by the student. It should be noted value to these devices is the collective learning for the visually impaired, both blind and low vision in people, as these devices allow the user to read the contents and even visually expand the contents to people with low vision. If we apply these benefits to our learning objects in electrical engineering and electronics will be facilitating innovative learning tool in devices that use on a daily basis.
Reduced Plasma Zinc Levels, Lipid Peroxidation, and Inflammation Biomarkers Levels in Hemodialysis Patients: Implications to Cardiovascular Mortality

Despite the fact that low plasma zinc (Zn) levels play important roles in the oxidative stress, the relationships between lipid peroxidation and inflammation biomarkers with low plasma Zn levels have not been investigated in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the Zn plasma levels, electronegative LDL [LDL(–)] levels, and inflammation markers as predictors of cardiovascular (CV) mortality in hemodialysis (HD) patients. Forty-five HD patients (28 men, 54.2 ± 12.7 years, 62.2 ± 51.4 months on dialysis and BMI 24.3 ± 4.1 kg/m2) were studied and compared to 20 healthy individuals (9 men, 51.6 ± 15.6 years, BMI 25.2 ± 3.9 kg/m2) and followed for 24 months to investigate the risks for CV mortality. LDL(–) levels were measured by ELISA, plasma Zn levels by atomic absorption spectrophotometry, C-reactive protein (CRP) level by immunoturbidimetric method, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) levels by a multiplex assay kit. HD patients presented low plasma Zn levels (54.9 ± 16.1 μg/dL) and high-LDL(–) (0.18 ± 0.12 U/L) and TNF-α (5.5 ± 2.2 pg/mL) levels when compared to healthy subjects (78.8 ± 9.4μ g/dL, 0.10 ± 0.08U/L, 2.4 ± 1.1 pg/mL, respectively, p < 0.05). Zn plasma levels were negatively correlated to TNF-α (r = –0.49; p = 0.0001) and LDL(–) (r = –0.33; p = 0.008). During the 2 years, 24.4% of the patients died, all due to CV disease. Analysis by the Cox model showed that high CRP, TNF-α, IL-6 levels, and long duration of HD were significant predictors of mortality. In conclusion, reduced Zn levels were associated with lipid peroxidation and inflammation, and we confirm here in a Brazilian cohort of HD patients that inflammation markers are strong predictors of CV death.
Nanomechanical properties and mineral concentration in articular calcified cartilage and subchondral bone

We studied articular calcified cartilage (ACC) and the immediately subchondral bone (SCB) in normal and osteoarthritic human femoral heads. Thick slices of human normal reference post mortem (PM) and osteoarthritic (OA) femoral heads (age 55–89 years) were embedded in PMMA, micromilled, carbon coated and studied using quantitative backscattered electron (qBSE) imaging to determine variations in degree of mineralization. With exact microanatomical location, nanoindentation was performed on the same block faces in representative superior (more highly loaded) and medial regions of the joint surface. Using a partial unloading method, elastic modulus as a function of indenter penetration depth was determined using a spherical tipped diamond indenter. A pointed indenter was used to determine the tissue hardness in selected locations. The relationship between mineralization and indentation modulus was more distinct in ACC than in SCB, the latter having a higher matrix concentration with variable collagen orientation. In OA, the bulk of the measurements were coincident with those in the PM samples, although there was a greater range in the levels of mineralization and modulus in ACC. In OA, extremely hypermineralized ACC was found in ACC proper, especially in superior regions, and translocated into SCB and hyaline cartilage. The very highly mineralized cartilage fragments may function as a hard grinding abrasive, accelerating wear rates whether attached to or fragmented from the eburnated surfaces of OA ACC. Highly mineralized regions would also alter loading patterns and thereby contribute to further destruction of the joint tissues.
Protective effects of rhubarb on experimental severe acute pancreatitis.

AIM To investigate the effects of rhubarb on severe acute pancreatitis (SAP) in rats. METHODS Severe acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 microg/kg body weight) plus 5-h restraint water-immersion stress. Rhubarb (75-150 mg/kg) was orally fed before the first cerulein injection. The degree of pancreatic edema, serum amylase level, local pancreatic blood flow (PBF), and histological alterations were investigated. The effects of rhubarb on pancreatic exocrine secretion in this model were evaluated by comparing with those of somatostatin. RESULTS In the Cerulein+Stress group, severe edema and diffuse hemorrhage in the pancreas were observed, the pancreatic wet weight (11.60+/-0.61 g/Kg) and serum amylase (458 490+/-43 100 U/L) were markedly increased (P<0.01 vs control). In the rhubarb (150 mg/kg) treated rats, necrosis and polymorphonuclear neutrophil (PMN) infiltration in the pancreas were significantly reduced (P<0.01), and a marked decrease (50%) in serum amylase levels was also observed (P<0.01). PBF dropped to 38% (93+/-5 mL/min per 100 g) of the control in the Cerulein+Stress group and partly recovered in the Cerulein+Stress+Rhubarb 150 mg group (135+/-12 mL/min per 100 g) (P<0.01). The pancreatic exocrine function was impaired in the SAP rats. The amylase levels of pancreatic juice were reduced in the rats treated with rhubarb or somatostatin, comparing with that of untreated SAP group. The bicarbonate concentration of pancreatic juice was markedly elevated only in the rhubarb-treated group (P<0.01). CONCLUSION Rhubarb can exert protective effects on SAP, probably by inhibiting the inflammation of pancreas, improving pancreatic microcirculation, and altering exocrine secretion.
The Purinergic System in Allotransplantation

The purine nucleotide adenosine triphosphate (ATP) is a universal source of energy for any intracellular reaction. Under specific physiological or pathological conditions, ATP can be released into extracellular spaces, where it binds and activates the purinergic receptors system (i.e. P2X, P2Y and P1 receptors). Extracellular ATP (eATP) binds to P2X or P2Y receptors in immune cells, where it mediates proliferation, chemotaxis, cytokine release, antigen presentation and cytotoxicity. eATP is then hydrolyzed by ectonucleotidases into adenosine diphosphate (ADP), which activates P2Y receptors. Ectonucleotidases also hydrolyze ADP to adenosine monophosphate and adenosine, which binds P1 receptors. In contrast to P2X and P2Y receptors, P1 receptors exert mainly an inhibitory effect on the immune response. In transplantation, a prominent role has been demonstrated for the eATP/P2X7R axis; the targeting of this pathway in fact is associated with long‐term graft function and reduced graft versus host disease severity in murine models. Novel P2X receptor inhibitors are available for clinical use and are under assessment as immunomodulatory agents. In this review, we will focus on the relevance of the purinergic system and on the potential benefits of targeting this system in allograft rejection and tolerance.