Miracle-dz/UniFAR-FTUs huggingface dataset:
Combinative therapeutic approach for better blood sugar level control in alloxan diabetic mice

In the present study the combined therapeutic approach of using an isolated compound from a herb and an oral hypoglycemic drug in alloxan-induced diabetic mice is investigated. Herbal drugs can have beneficial effects in terms of reducing the dosage, side effects and duration of action of synthetic drugs. The results show that combined therapy with 4hydroxyisoleucine and pioglitazone is more beneficial than pioglitazone alone and also more beneficial than the combination of 4 hydroxyisoleucine and glyburide in the treatment of diabetes. (Int J Diabetes Metab 14: 104-105, 2006)
Contribution of land‐atmosphere coupling to recent European summer heat waves

Most of the recent European summer heat waves have been preceded by a pronounced spring precipitation deficit. The lack of precipitation and the associated depletion of soil moisture result in reduced latent cooling and thereby amplify the summer temperature extremes. In order to quantify the contribution of land‐atmosphere interactions, we conduct regional climate simulations with and without land‐atmosphere coupling for four selected major summer heat waves in 1976, 1994, 2003, and 2005. The coupled simulation uses a fully coupled land‐surface model, while in the uncoupled simulation the mean seasonal cycle of soil moisture is prescribed. The experiments reveal that land‐atmosphere coupling plays an important role for the evolution of the investigated heat waves both through local and remote effects. During all simulated events soil moisture‐temperature interactions increase the heat wave duration and account for typically 50–80% of the number of hot summer days. The largest impact is found for daily maximum temperatures during heat wave episodes.
Impact of Empirical-Therapy Selection on Outcomes of Intravenous Drug Users with Infective Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus

ABSTRACT This study compares beta-lactam and vancomycin among intravenous drug users with infective endocarditis caused by methicillin-susceptible Staphylococcus aureus. Patients who received vancomycin had higher infection-related mortality, even if they were switched to beta-lactam once culture results became available; this relationship persisted after logistic regression analysis controlling for clinical characteristics.
Integration of the nasal complex: Implications for developmental and evolutionary change in modern humans.

OBJECTIVES Assessing the strength of integration among different regions of the modern human nasal complex is important for developing a more thorough understanding of the determinants of nasal morphology. Given the morphogenetic influence of cartilage on adjacent intramembranous growth sites, the interaction between chondrocranial- versus intramembranous-derived nasal structures may have a significant influence on patterns of nasal variation. The purpose of this study is to examine integration between the chondrocranial- and intramembranous-derived regions of the nasal complex. MATERIALS AND METHODS Using computed tomograph (CT) scans, we collected three-dimensional coordinate landmark data from a static adult sample (n = 62). First, using centroid size, and the symmetric and asymmetric components of shape variation, we examined the strength of integration between landmarks representing chondrocranial-derived structures (e.g., ethmoid, external nasal cartilages) and landmarks representing intramembranous-derived structures (nasal floor, anterior nasal aperture, etc.). Second, given that the strength of integration is a relative measure, we compared integration between chondrocranial- and intramembranous-derived structures to the more modularized external and internal regions of the nasal complex. RESULTS There was significant moderate morphological integration between chondrocranial- versus intramembranous-derived regions of the nasal complex. Moreover, integration between chondrocranial- versus intramembranous-derived structures was consistently stronger when compared to external versus internal regions for both the symmetric and asymmetric components of variation. Thus, more covariation within the nasal complex could be explained by the relationship between chondrocranial- and intramembranous-derived structures. CONCLUSIONS Our results suggest that the interaction between chondrocranial- and intramembranous-derived structures may be an important determinant in the patterning of nasal complex variation.
Salmonella enterica Serovar Enteritidis Enterocolitis during Late Stages of Gestation Induces an Adverse Pregnancy Outcome in the Murine Model

Foodborne diseases caused by Salmonella enterica serovar Enteritidis (S. Enteritidis) are a significant health problem. Pregnancy, state of immunological tolerance, is a predisposing condition for the development of infections with intracellular pathogens. Salmonella species can cause pregnancy complications such as chorioamnionitis, transplacental fetal infection, pre term labor, abortions, neonatal and maternal septicemia. However, the specific mechanisms by which Salmonella infections trigger these alterations are not clear. In the present work, using a self-limiting enterocolitis murine model, we show that the ingestion of a low dose of S. Enteritidis at late stages of pregnancy (day 15 of gestation) is sufficient to induce massive maternal infection. We found that Salmonella infection leads to 40% of pre term delivery, 33% of abortion and fetal growth restriction. Placental dysfunction during S. Enteritidis enterocolitis was confirmed through cellular infiltration and hypoxia markers (MPO activity and COX-1 and COX-2 expression, respectively). Apoptosis in placental tissue due to Salmonella infection was also evident at day 18 of gestation when investigated by morphometric procedure, DNA fragmentation and Fas/FasL expression. Also, the expression of IFN-γ, TNF-α, IL-17 and IL-10 was up regulated in response to Salmonella not only in placenta, but also in amniotic fluid and maternal serum. Altogether, our results demonstrate that S. Enteritidis enterocolitis during late stages of gestation causes detrimental effect on pregnancy outcome.
Preparation and Evaluation of Valdecoxib Emulgel Formulations.

Microemulsion based emulgel formulations of valdecoxib was developed by using ethyl oleate (EO) as oil, tween-80 in different proportions with propylene glycol (PG) as surfactant/ co-surfactant along with water and incorporated into carbopol 940 as gellant.Microemulsions were characterized for optical birefringence, globule size, polydispersity andconductivity. All microemulsion were stable, transparent, oil in water type and in globulesize range of 12.4-15.3nm. The prepared emulgels were evaluated for pH, drug content,viscosity, in vitro drug release study using dialysis membrane, and skin irritationtest. The pH and drug content of emulgels was in acceptable range of topical application. The viscosity was increased as the proportion of tween-80 and ethyl oleate increased. The in vitro release of valdecoxib was also increased as the proportion of tween-80 increased. Therelease was in the order of 3:1>2:1>1:1 ratios of tween-80 to PG. The release obeys Higuchi’s diffusion equation and follows first order kinetics.All the emulgels were free from skin irritation and were stable at room temperature. From the study it can be concluded that microemulsion based emulgel formulation containing tween-80: PG in the proportion of 3:1 was the best formulation.
Oxygen isotope analysis of levoglucosan, a tracer of wood burning, in experimental and ambient aerosol samples.

RATIONALE Levoglucosan is formed from cellulose during biomass burning. It is therefore often used as a specific tracer to quantify the contribution of wood burning to the aerosol loading. The stable oxygen isotope composition (δ18 O value) of biomass is determined by the water cycle and varies regionally, and hence the δ18 O value of levoglucosan could help to identify source regions of organic aerosols. METHODS After solvent extraction of the organic fraction and concentration steps, a recently developed methylation derivatisation technique was applied on experimental (i.e. controlled wood-burning experiments) and on ambient aerosol samples from Switzerland and Lithuania. The method achieves sufficient compound separation for isotope analysis in atmospheric particulate matter, enabling δ18 O analysis of levoglucosan by gas chromatography/pyrolysis-isotope ratio mass spectrometry (GC/Pyr-IRMS), with a precision better than 1.0 ‰ and an accuracy of 0.3 ‰. RESULTS The δ18 O value of the levoglucosan released during controlled wood-burning experiments was not significantly different from the cellulose δ18 O values, which implies very little or no isotope fractionation during wood burning under the given conditions. While the δ18 O values of levoglucosan in Swiss samples were as expected for the source region, those in Lithuania were 1-4 ‰ lower than expected. This may be due to differences in vegetation (grass vs wood) or burning conditions (high vs low temperatures). CONCLUSIONS Low oxygen isotope fractionation between cellulose and levoglucosan and clear differences in levoglucosan δ18 O values between the Swiss and Lithuanian ambient samples demonstrate that our new method is useful for source appointment studies on wood-burning-derived aerosols.
Detection of Memory B Activity Against a Therapeutic Protein in Treatment-Naïve Subjects

Bridging immunoassays commonly used to detect and characterize immunogenicity during biologic development do not provide direct information on the presence or development of a memory anti-drug antibody (ADA) response. In this study, a B cell ELISPOT assay method was used to evaluate pre-existing ADA for anti-TNFR1 domain antibody, GSK1995057, an experimental biologic in treatment naive subjects. This assay utilized a 7-day activation of PBMCs by a combination of GSK1995057 (antigen) and polyclonal stimulator followed by GSK1995057-specific ELISPOT for the enumeration of memory B cells that have differentiated into antibody secreting cells (ASC) in vitro. We demonstrated that GSK1995057-specific ASC were detectable in treatment-naïve subjects with pre-existing ADA; the frequency of drug-specific ASC was low and ranged from 1 to 10 spot forming units (SFU) per million cells. Interestingly, the frequency of drug-specific ASC correlated with the ADA level measured using an in vitro ADA assay. We further confirmed that the ASC originated from CD27+ memory B cells, not from CD27−-naïve B cells. Our data demonstrated the utility of the B cell ELISPOT method in therapeutic protein immunogenicity evaluation, providing a novel way to confirm and characterize the cell population producing pre-existing ADA. This novel application of a B cell ELISPOT assay informs and characterizes immune memory activity regarding incidence and magnitude associated with a pre-existing ADA response.
Increased Expression of GOLPH3 is Associated with the Proliferation of Prostate Cancer

Background: Golgi phosphoprotein 3 (GOLPH3) is a metastasis-associated gene, however its role in cell proliferation of prostate cancer (PCa) has not yet been elucidated. Methods: The level of expression of GOLPH3 and other genes was examined by quantitative real-time PCR (QPCR) and western blot analysis. Furthermore, we performed a comprehensive analysis of the expression of GOLPH3 in PCa using a tissue microarray (TMA) and correlated our findings with pathological parameters of PCa. RNA interference (RNAi) was used to silence the expression of GOLPH3 in PC-3 cells and to measure the effects on proliferation and cell cycle using the CCK-8 assay and flow cytometry. Western blots were also employed to assess AKT-mTOR and cell cycle-related proteins. Results: We showed that the expression of GOLPH3 was located at the trans-Golgi membranes in PCa cells. We found that GOLPH3 was expressed in all PCa cells and was significantly higher in two androgen-independent cell lines, DU145 and PC-3. TMA immunohistochemistry showed that GOLPH3 was positive in 64% of cancer tissue samples compared with 20% in normal and 30% in benign samples (P<0.05). In vitro, silencing GOLPH3 expression inhibited cell proliferation and arrested the cell cycle at the G2/M phase. Silencing GOLPH3 also activated P21 expression but suppressed the expression of CDK1/2 and cyclinB1 protein together with the phosphorylation of AKT and mTOR. Conclusions: The expression of the GOLPH3 protein was significantly elevated in PCa. GOLPH3 can promote cell proliferation by enhancing the activity of AKT-mTOR signaling. Altogether, these findings suggest that GOLPH3 play important roles in proliferation and cell cycle regulation in PCa and might serve as promising biomarkers for PCa progression as well as potential therapeutic targets.
Variable exposure and immunological response to Lyme disease Borrelia among North Atlantic seabird species

Colonial seabirds often breed in large aggregations. These individuals can be exposed to parasitism by the tick Ixodes uriae, but little is known about the circulation of pathogens carried by this ectoparasite, including Lyme disease Borrelia. Here we investigated the prevalence of antibodies (Ab) against Borrelia burgdorferi sensu lato in seabird species sampled at eight locations across the North Atlantic. Using enzyme-linked immunosorbent assay tests, we found that the prevalence of anti-Borrelia Ab in adult seabirds was 39.6% on average (over 444 individuals), but that it varied among colonies and species. Common guillemots showed higher seroprevalence (77.1%±5.9) than black-legged kittiwakes (18.6%±6.7) and Atlantic puffins (22.6%±6.3). Immunoblot-banding patterns of positive individuals, reflecting the variability of Borrelia antigens against which Ab were produced, also differed among locations and species, and did not tightly match the prevalence of Borrelia phylogroups previously identified in ticks collected from the same host individuals. These results represent the first report of the widespread prevalence of Ab against Borrelia within an assemblage of seabird species and demonstrate that Borrelia is an integrated aspect in the interaction between seabirds and ticks. More detailed studies on the dynamics of Borrelia within and among seabird species at different spatial scales will now be required to better understand the implications of this interaction for seabird ecology and the epidemiology of Lyme disease.
Mechanical Properties of Sugarcane Stalk

The study was undertaken to assess the mechanical properties including compressive and shearing strength of sugarcane (Saccharum officinarum L.) stalks for four varieties viz., Co99004,CoC-671,Co-85004 and Co-86032. The highest value of compressive strength (47.75 kN) at lower section was recorded for the variety Co-86032, whereas the lowest value (34 kN) was obtained with Co-85004. The maximum value of compressive strength for top section (49.25 kN) was recorded with CoC-671 and the minimum (39.75 kN) for the variety Co-99004. The cutting force required for shearing sugarcane stalk, ultimate cutting stress and specific shearing energy were determined at two sections for all the four varieties. It was observed that the maximum value of shearing force (1333.89 N) would be observed for the variety Co85004 at lower section and it was (815.29 N) recorded for the variety CoC-671.The maximum value of ultimate cutting stress was (1.98 MPa) with Co-85004 at the lower section, while it was minimum (1.05 MPa) for the variety Co-99004. Similarly, the maximum value of specific shearing energy (39.68 mJ/mm2 ) was recorded for the variety Co-85004 for the lower section, while it was minimum (13.06 mJ/mm2 ) with CoC-671.
Scars in depression: is a conceptual shift necessary to solve the puzzle?

Although clinical findings suggest that in the aftermath of depression a process of ‘scarring’ may ensue, research examining the issue of ‘scars’ (including biological, psychological and cognitive changes) has remained largely inconclusive. This paper proposes a new approach to the concept of ‘scars’ that is (i) based on a dimensional view of depression, (ii) uses methods that take into account the dynamic interplay between the person and his context, (iii) differentiates between scars following depression and scars following the factor that actually caused the depression such as stress and (iv) introduces a dynamic view of the concept of ‘scars’ in that it hypothesizes that scars can wax and wane. This approach may stimulate the discovery of new entries in the puzzle underlying the ontogenesis of vulnerability and resilience. Furthermore, it may provide insights that help to develop new therapies for depression.
INTERACTION EFFECTS OF POSTURE AND UNEVEN GROUND ON ABLE-BODIED WALKING KINETICS

Interactions between trunk orientation and gait kinetics are proposed to be inevitable for maintaining dynamic balance, and these interactions are unknown for walking on uneven ground. The purpose of this study was to investigate the interaction effects of posture (regular erect, 30°, 50° and 70° trunk flexion) and step category (unperturbed, perturbation, preand post-perturbation) on able-bodied walking kinetics. Statistical analysis revealed interactions posture×step: with increased trunk flexion, walking on uneven ground exhibited less changes in GRF kinetic parameters relative to upright walking. Pre-adaptations were more pronounced in the approach step to the drop in regular erect gait. It seems that in trunk-flexed gaits trunk is used in a compensatory way during the step-down to accommodate changes in ground level. In conclusion, exploitation of this mechanism resembles the ability of small birds in adjusting their zigzag-like configured legs to cope with changes in ground level.
Maximum likelihood from incomplete data via the EM - algorithm plus discussions on the paper

Vibratory power unit for vibrating conveyers and screens comprising an asynchronous polyphase motor, at least one pair of associated unbalanced masses disposed on the shaft of said motor, with the first mass of a pair of said unbalanced masses being rigidly fastened to said shaft and with said second mass of said pair being movably arranged relative to said first mass, means for controlling and regulating the conveying rate during conveyer operation by varying the rotational speed of said motor between predetermined minimum and maximum values, said second mass being movably outwardly by centrifugal force against the pressure of spring means, said spring means being prestressed in such a manner that said second mass is, at rotational motor speeds lower than said minimum speed, held in its initial position, and at motor speeds between said lower and upper values in positions which are radially offset with respect to the axis of said motor to an extent depending on the value of said rotational motor speed.
Protein Intake and Mobility Limitation in Community‐Dwelling Older Adults: the Health ABC Study

The current Recommended Dietary Allowance (RDA) for protein is based on short‐term nitrogen balance studies in young adults and may underestimate the amount needed to optimally preserve physical function in older adults. We examined the association between protein intake and the onset of mobility limitation over 6 years of follow‐up in older adults in the Health ABC study.
High phenolics Rutgers Scarlet Lettuce improves glucose metabolism in high fat diet-induced obese mice.

SCOPE The ability of high phenolic Rutgers Scarlet Lettuce (RSL) to attenuate metabolic syndrome and gut dysbiosis was studied in very high fat diet (VHFD)-fed mice. Phenolic absorption was assessed in vivo and in a gastrointestinal tract model. METHODS AND RESULTS Mice were fed VHFD, VHFD supplemented with RSL (RSL-VHFD) or store-purchased green lettuce (GL-VHFD), or low-fat diet (LFD) for 13 weeks. Compared to VHFD or GL-VHFD-fed groups, RSL-VHFD group showed significantly improved oral glucose tolerance (p<0.05). Comparison of VHFD, RSL-VHFD, and GL-VHFD groups revealed no significant differences with respect to insulin tolerance, hepatic lipids, body weight gain, fat mass, plasma glucose, triglycerides, free fatty acid, and lipopolysaccharide levels, as well as relative abundances of major bacterial phyla from 16S rDNA amplicon data sequences (from fecal and cecal samples). However, RSL and GL-supplementation increased abundance of several taxa involved in plant polysaccharide degradation/fermentation. RSL phenolics chlorogenic acid, quercetin-3-glucoside, and quercetin-malonyl-glucoside were bioaccessible in the TIM-1 digestion model, but had relatively low recovery. CONCLUSIONS RSL phenolics contributed to attenuation of post-prandial hyperglycemia. Changes in gut microbiota were likely due to microbiota accessible carbohydrates in RSL and GL rather than RSL phenolics, which may be metabolized, absorbed, or degraded before reaching the colon.
Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges

Significance Nanotunnels are long, thin mitochondrial extensions that have been implied in direct long-distance (1 to >5 µm) communication between mitochondria of cardiac myocytes. The engineered RyR2A4860G+/− mutation, resulting in loss of function of the sarcoplasmic reticulum calcium release channel and arrhythmia, induces a striking increase in the frequency of long-distance intermitochondrial communication via nanotunnels without involvement of obvious mitochondrial migration. We use this model for exploring the significance of mitochondrial nanotunneling in myocardium and the contribution of microtubules to the formation of these unusual organelle extensions using EM tomography and live confocal imaging. This study constitutes an approach to arrhythmia investigations that focuses on a new target: the mitochondria. Exchanges of matrix contents are essential to the maintenance of mitochondria. Cardiac mitochondrial exchange matrix content in two ways: by direct contact with neighboring mitochondria and over longer distances. The latter mode is supported by thin tubular protrusions, called nanotunnels, that contact other mitochondria at relatively long distances. Here, we report that cardiac myocytes of heterozygous mice carrying a catecholaminergic polymorphic ventricular tachycardia-linked RyR2 mutation (A4860G) show a unique and unusual mitochondrial response: a significantly increased frequency of nanotunnel extensions. The mutation induces Ca2+ imbalance by depressing RyR2 channel activity during excitation–contraction coupling, resulting in random bursts of Ca2+ release probably due to Ca2+ overload in the sarcoplasmic reticulum. We took advantage of the increased nanotunnel frequency in RyR2A4860G+/− cardiomyocytes to investigate and accurately define the ultrastructure of these mitochondrial extensions and to reconstruct the overall 3D distribution of nanotunnels using electron tomography. Additionally, to define the effects of communication via nanotunnels, we evaluated the intermitochondrial exchanges of matrix-targeted soluble fluorescent proteins, mtDsRed and photoactivable mtPA-GFP, in isolated cardiomyocytes by confocal microscopy. A direct comparison between exchanges occurring at short and long distances directly demonstrates that communication via nanotunnels is slower.