Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of intracellular anion superoxide level, heat shock protein A2 and protamine positive spermatozoa percentages in teratoasthenozoospermia

Background: Teratoasthenozoospermia (TA) is a severe form of male infertility with no clear etiology. Objective: To compare the level of intracellular anion superoxide (O2–), heat shock protein A2 (HSPA2) and protamine deficiencies in ejaculated spermatozoa between teratoasthenozoospermic and normozoospermic men. Materials and Methods: In this case- control study, semen samples of 20 infertile men, with TA (with normal morphology lower than 4%_ and total motility lower than 40% ) as the case group and 20 normozoospermic fertile men as the control group were evaluated for intracellular O2– and HSPA2 by flow cytometry and protamine deficiency by Chromomycin A3 (CMA3) test. Results: The rate of CMA3+ spermatozoa in the case group was higher than controls (p=0.001). The percentages of HSPA2+ spermatozoa in the cases were significantly lower than controls (p=0.001). Also, intracellular O2– levels in the case group were significantly higher than controls (p=0.001) and had positive correlations with sperm apoptosis (r=0.79, p=0.01) and CMA3 positive sperm (r=0.76, p=0.01), but negative correlations with normal morphology (r=-0.81, p=0.01) and motility (r=-0.81, p=0.01). There was no significant correlation between intracellular O2– and HSPA2 in the case group (r=0.041, p=0.79). Conclusion: We suggest that the increase in intracellular O2–, decrease in spermatozoa HSPA2+, and high percentages of spermatozoa with immature chromatin might be considered as etiologies of infertility in TA patients.
A New Approach to Evaluate the Total Reserve of Hematopoietic Progenitors after Acute Irradiation

Abstract Grande, T. and Bueren, J. A. A New Approach to Evaluate the Total Reserve of Hematopoietic Progenitors after Acute Irradiation. Radiat. Res. 162, 397–404 (2004). Based on the capacity of certain hematopoietic growth factors to mobilize the hematopoietic progenitors from bone marrow to peripheral blood, we have investigated whether the number of progenitors that can be mobilized to peripheral blood after irradiation correlates with the radiation dose and reflects the total reserve of bone marrow progenitors that survive the exposure. In three different mouse strains, a close relationship was observed between the number of G-CSF mobilized progenitors and the radiation dose received by the animals. When G-CSF was replaced by one single injection of SD01 plus thrombopoietin, a similar relationship between the two parameters was observed, which fitted to the multitarget theoretical model. This treatment also promoted 50% survival in mice receiving a lethal dose of 9 Gy. The estimation of the total number of CFU-GM progenitors in the irradiated mice also allowed us to establish a good relationship between the number of progenitors that were mobilized to peripheral blood with respect to the global reserve of surviving progenitors. These results suggest that the quantification of mobilized hematopoietic progenitors would predict the severity and reversibility of the hematopoietic syndrome of irradiated victims, based on direct estimations of their global reserve of hematopoietic progenitors and stem cells.
Adult onset Still's disease: clinical presentation in a large cohort of Italian patients.

OBJECTIVES To characterise the clinical phenotype of Italian patients with adult-onset Still's disease (AOSD). METHODS Sixty-six subjects who received a definite diagnosis of AOSD were seen and followed-up at our institution from 1991 to 2009. The diagnosis was made by a senior rheumatologist and confirmed by Yamaguchi's criteria for AOSD. Data regarding clinical manifestations, laboratory and radiographic features, and disease course were collected and compared with those reported in other published series of different ethnicity. RESULTS The most frequent features were: articular pain (100%), acute phase reactants elevation (100%), elevated serum ferritin (97%), high fever (95%), negative RF and ANA (92%), neutrophilia (82%), skin rash (79%), and overt arthritis (79%). Forty-percent of patients showed a chronic articular disease. Five subjects (8%) experienced severe, life-threatening complications, and 1 patient died. As compared to other North American, North European, Middle Eastern, and Far Eastern cohorts, Italian patients showed significant differences in several epidemiologic, clinical and laboratory features. CONCLUSIONS Our data show that AOSD is rare in the Italian population, and that its clinical presentation appears to be significantly influenced by the ethnicity of the affected patients. Given its broad differential diagnosis, early recognition of this condition is challenging, but it could become crucial in the setting of severe complications. Beyond the protean manifestations of this disease, a clinical picture of seronegative febrile arthritis and skin rash, concurrent with a marked elevation in serum ferritin should always be mindful of AOSD.
Relationships Among Microbial Communities, Maternal Cells, Oligosaccharides, and Macronutrients in Human Milk

Background: Human milk provides all essential nutrients necessary for early life and is rich in nonnutrients, maternally derived (host) cells, and bacteria, but almost nothing is known about the interplay among these components. Research aim: The primary objective of this research was to characterize relationships among macronutrients, maternal cells, and bacteria in milk. Methods: Milk samples were collected from 16 women and analyzed for protein, lipid, fatty acid, lactose, and human milk oligosaccharide concentrations. Concentrations of maternal cells were determined using microscopy, and somatic cell counts were enumerated. Microbial ecologies were characterized using culture-independent methods. Results: Absolute and relative concentrations of maternal cells were mostly consistent within each woman as were relative abundances of bacterial genera, and there were many apparent relationships between these factors. For instance, relative abundance of Serratia was negatively associated with somatic cell counts (r = –.47, p < .0001) and neutrophil concentration (r = –.38, p < .0006). Concentrations of several oligosaccharides were correlated with maternally derived cell types as well as somatic cell counts; for example, lacto-N-tetraose and lacto-N-neotetraose were inversely correlated with somatic cell counts (r = –.64, p = .0082; r = –.52, p = .0387, respectively), and relative abundance of Staphylococcus was positively associated with total oligosaccharide concentration (r = .69, p = .0034). Complex relationships between milk nutrients and bacterial community profile, maternal cells, and milk oligosaccharides were also apparent. Conclusion: These data support the possibility that profiles of maternally derived cells, nutrient concentrations, and the microbiome of human milk might be interrelated.
'It's the little things that count': healthcare professionals' views on delivering dignified care: a qualitative study.

AIMS To explore healthcare professionals' perspectives of dignified care and experiences of providing care. BACKGROUND Although 'care' and dignity in care are seen as central to the delivery of good care by patients, families and professionals, we still lack a clear understanding of what these, often contested and elusive concepts, mean in the practice setting, particularly from the perspective of healthcare professionals. DESIGN Interview based qualitative research design. METHODS In-depth interviews were conducted with healthcare professionals working in four UK NHS trusts. Data were collected between June-November 2012. Interviews were audio-recorded, transcribed and analysed using thematic analysis. FINDINGS Forty-eight healthcare professionals took part in this interview based study. Two main themes that encapsulated how care and dignity in care is enacted by professionals were identified: focusing on the 'little' things that matter to both professionals and patients; and improving care by making poor care 'visible'. CONCLUSION Our findings show that the 'little things' in care allow professionals to 'care for' but also 'care about' patients, suggesting that these two aspects of caring become intrinsically interlinked. Our findings also suggest that 'making poor care visible' challenges engrained and task rather than human focused care in a non-threatening way, which can be the catalyst for providing care that is caring and dignified.
Particles from wood smoke and road traffic differently affect the innate immune system of the lung

The effect of particles from road traffic and wood smoke on the innate immune response in the lung was studied in a lung challenge model with the intracellular bacterium Listeria monocytogenes. Female Balb/cA mice were instilled intratracheally with wood smoke particles, particles from road traffic collected during winter (studded tires used; St+), and during autumn (no studded tires; St−), or diesel exhaust particles (DEP). Simultaneously with, and 1 or 7 days after particle instillation, 105 bacteria were inoculated intratracheally. Bacterial numbers in the lungs and spleen 1 day after Listeria challenge were determined, as an indicator of cellular activation. In separate experiments, bronchoalveolar lavage (BAL) fluid was collected 4 h and 24 h after particle instillation. All particles tested reduced the numbers of bacteria in the lung 24 h after bacterial inoculation. When particles were given simultaneously with Listeria, the reduction was greatest for DEP, followed by St+ and St−, and least for wood smoke particles. Particle effects were no longer apparent after 7 days. Neutrophil numbers in BAL fluid were increased for all particle exposed groups. St+ and St− induced the highest levels of IL-1β, MIP-2, MCP-1, and TNF-α, followed by DEP, which induced no TNF-α. In contrast, wood smoke particles only increased lactate dehydrogenase (LDH) activity, indicating a cytotoxic effect of these particles. In conclusion, all particles tested activated the innate immune system as determined with Listeria. However, differences in kinetics of anti-Listeria activity and levels of proinflammatory mediators point to cellular activation by different mechanisms.
Pollen movement in declining populations of California Valley oak, Quercus lobata: where have all the fathers gone?

The fragmented populations and reduced population densities that result from human disturbance are issues of growing importance in evolutionary and conservation biology. A key issue is whether remnant individuals become reproductively isolated. California Valley oak (Quercus lobata) is a widely distributed, endemic species in California, increasingly jeopardized by anthropogenic changes in biota and land use. We studied pollen movement in a savannah population of Valley oak at Sedgwick Reserve, Santa Barbara County, to estimate effective number of pollen donors (Nep) and average distance of effective pollen movement (δ). Using twogener, our recently developed hybrid model of paternity and genetic structure treatments that analyses maternal and progeny multilocus genotypes, we found that current Nep = 3.68 individuals. Based on an average adult density of d= 1.19 stems/ha, we assumed a bivariate normal distribution to model current average pollen dispersal distance (δ) and estimated δ= 64.8 m. We then deployed our parameter estimates in spatially explicit models of the Sedgwick population to evaluate the extent to which Nep may have changed, as a consequence of progressive stand thinning between 1944 and 1999. Assuming that pollen dispersal distance has not changed, we estimate Nep was 4.57 individuals in 1944, when stand density was 1.48. Both estimates indicate fewer effective fathers than one might expect for wind‐pollinated species and fewer than observed elsewhere. The results presented here provide a basis for further refinements on modelling pollen movement. If the trends continue, then ongoing demographic attrition could further reduce neighbourhood size in Valley oak resulting in increased risk of reproductive failure and genetic isolation.
Down-Regulation of a SILENT INFORMATION REGULATOR2-Related Histone Deacetylase Gene, OsSRT1, Induces DNA Fragmentation and Cell Death in Rice1[C][W]

The SILENT INFORMATION REGULATOR2 (SIR2) family proteins are NAD+-dependent histone deacetylases. Sir2 is involved in chromatin silencing at the mating-type loci, rDNA, and telomeres in yeast and is associated with lifespan extension in yeast, worms, and flies, but also in a broader range of additional functions. In this work, we investigated the role of OsSRT1, one of the two SIR2-related genes found in rice (Oryza sativa). We show that OsSRT1 is a widely expressed nuclear protein with higher levels in rapidly dividing tissues. OsSRT1 RNA interference induced an increase of histone H3K9 (lysine-9 of H3) acetylation and a decrease of H3K9 dimethylation, leading to H2O2 production, DNA fragmentation, cell death, and lesions mimicking plant hypersensitive responses during incompatible interactions with pathogens, whereas overexpression of OsSRT1 enhanced tolerance to oxidative stress. Transcript microarray analysis revealed that the transcription of many transposons and retrotransposons in addition to genes related to hypersensitive response and/or programmed cell death was activated. Chromatin immunoprecipitation assays showed that OsSRT1 down-regulation induced histone H3K9 acetylation on the transposable elements and some of the hypersensitive response-related genes, suggesting that these genes may be among the primary targets of deacetylation regulated by OsSRT1. Our data together suggest that the rice SIR2-like gene is required for safeguard against genome instability and cell damage to ensure plant cell growth, but likely implicates different molecular mechanisms than yeast and animal homologs.
Similar Interactions of the Poliovirus and Rhinovirus 3D Polymerases with the 3′ Untranslated Region of Rhinovirus 14

ABSTRACT We showed previously that a human rhinovirus 14 (HRV14) 3′ untranslated region (3′ UTR) on a poliovirus genome was able to replicate with nearly wild-type kinetics (J. B. Rohll, D. H. Moon, D. J. Evans, and J. W. Almond, J. Virol 69:7835–7844, 1995). This enabled the HRV14 single 3′ UTR stem-loop structure to be studied in combination with a sensitive reporter system, poliovirus FLC/REP, in which the capsid coding region is replaced by an in-frame chloramphemicol acetyltransferase (CAT) gene. Using such a construct, we identified a mutant (designated mut4), in which the structure and stability of the stem were predicted to be maintained, that replicated very poorly as determined by its level of CAT activity. The effect of this mutant 3′ UTR on replication has been further investigated by transferring it onto the full-length cDNAs of both poliovirus type 3 (PV3) and HRV14. Virus was recovered with a parental plaque phenotype at a low frequency, indicating the acquisition of compensating changes, which sequence analysis revealed were, in both poliovirus- and rhinovirus-derived viruses, located in the active-site cleft of 3D polymerase and involved the substitution of Asn18 for Tyr. These results provide further evidence of a specific interaction between the 3′ UTR of picornaviruses and the viral polymerase and also indicate similar interactions of the 3′ UTR of rhinovirus with both poliovirus and rhinovirus polymerases.
BDNF‐mediated modulation of GABA and glycine release in dorsal horn lamina II from postnatal rats

Recent studies show that excitatory glutamatergic transmission is potentiated by BDNF in superficial dorsal horn, both at the pre‐ and the postsynaptic site. The role of BDNF in modulating GABA and glycine‐mediated inhibitory transmission has not been fully investigated. To determine whether the neurotrophin is effective in regulating the spontaneous release of the two neurotransmitters, we have recorded miniature inhibitory postsynaptic currents (mIPSCs) in lamina II of post‐natal rats. We show that application of BDNF enhanced the spontaneous release of GABA and glycine, in presence of tetrodotoxin. The effect was blocked by the trk‐receptor inhibitor k‐252a. Amplitude and kinetics of mIPSCs were not altered. Evoked GABA and glycine IPSCs (eIPSCs) were depressed by BDNF and the coefficient of variation of eIPSC amplitude was significantly increased. By recording glycine eIPSCs with the paired‐pulse protocol, an increase of paired‐pulse ratio during BDNF application was observed. We performed parallel ultrastructural studies to unveil the circuitry involved in the effects of BDNF. These studies show that synaptic interactions between full length functional trkB receptors and GABA‐containing profiles only occur at non peptidergic synaptic glomeruli of types I and II. Expression of trkB in presynaptic vesicle‐containing dendrites originating from GABAergic islet cells, indicates these profiles as key structures in the modulation of inhibitory neurotransmission by the neurotrophin. Our results thus describe a yet uncharacterized effect of BDNF in lamina II, giving further strength to the notion that the neurotrophin plays an important role in pain neurotransmission. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
RXLR-Mediated Entry of Phytophthora sojae Effector Avr1b into Soybean Cells Does Not Require Pathogen-Encoded Machinery[W]

Effector proteins secreted by oomycete and fungal pathogens have been inferred to enter host cells, where they interact with host resistance gene products. Using the effector protein Avr1b of Phytophthora sojae, an oomycete pathogen of soybean (Glycine max), we show that a pair of sequence motifs, RXLR and dEER, plus surrounding sequences, are both necessary and sufficient to deliver the protein into plant cells. Particle bombardment experiments demonstrate that these motifs function in the absence of the pathogen, indicating that no additional pathogen-encoded machinery is required for effector protein entry into host cells. Furthermore, fusion of the Avr1b RXLR-dEER domain to green fluorescent protein (GFP) allows GFP to enter soybean root cells autonomously. The conclusion that RXLR and dEER serve to transduce oomycete effectors into host cells indicates that the >370 RXLR-dEER–containing proteins encoded in the genome sequence of P. sojae are candidate effectors. We further show that the RXLR and dEER motifs can be replaced by the closely related erythrocyte targeting signals found in effector proteins of Plasmodium, the protozoan that causes malaria in humans. Mutational analysis of the RXLR motif shows that the required residues are very similar in the motifs of Plasmodium and Phytophthora. Thus, the machinery of the hosts (soybean and human) targeted by the effectors may be very ancient.
Characteristics of autobiographical memories and prospective imagery across a spectrum of hypomanic personality traits

Evidence of a strong causal relationship between mental imagery and emotion has informed psychological conceptualisations of disordered positive mood states (i.e., mania). Holmes et al.'s cognitive model of bipolar disorder asserts a prominent role for intrusive and affect-laden positive imagery of the past and the future in the amplification and maintenance of positive mood and associated manic behaviours. The aims of the current study were two-fold: (1) to test aspects of this model in a non-clinical population sampled for hypomanic personality traits and (2) to examine the phenomenological characteristics of positive autobiographical memories and imagery of the future. Undergraduate students (N = 80) completed a battery of self-report questionnaires and rated their positive and negative memories and images of the future on a number of dimensions. We found significant positive correlations between hypomanic tendencies and the (1) everyday experience and use of mental imagery, (2) experience of intrusive mental imagery of future events, (3) emotional intensity and sensory detail of positive but not negative autobiographical memories. Results are discussed in the context of their theoretical and clinical implications, and directions for future research are considered.
A Determinant of Sindbis Virus Neurovirulence Enables Efficient Disruption of Jak/STAT Signaling

ABSTRACT Previous studies with Venezuelan equine encephalitis virus and Sindbis virus (SINV) indicate that alphaviruses are capable of suppressing the cellular response to type I and type II interferons (IFNs) by disrupting Jak/STAT signaling; however, the relevance of this signaling inhibition toward pathogenesis has not been investigated. The relative abilities of neurovirulent and nonneurovirulent SINV strains to downregulate Jak/STAT signaling were compared to determine whether the ability to inhibit IFN signaling correlates with virulence potential. The adult mouse neurovirulent strain AR86 was found to rapidly and robustly inhibit tyrosine phosphorylation of STAT1 and STAT2 in response to IFN-γ and/or IFN-β. In contrast, the closely related SINV strains Girdwood and TR339, which do not cause detectable disease in adult mice, were relatively inefficient inhibitors of STAT1/2 activation. Decreased STAT activation in AR86-infected cells was associated with decreased activation of the IFN receptor-associated tyrosine kinases Tyk2, Jak1, and Jak2. To identify the viral factor(s) involved, we infected cells with several panels of AR86/Girdwood chimeric viruses. Surprisingly, we found that a single amino acid determinant, threonine at nsP1 position 538, which is required for AR86 virulence, was also required for efficient disruption of STAT1 activation, and this determinant fully restored STAT1 inhibition when it was introduced into the avirulent Girdwood background. These data indicate that a key virulence determinant plays a critical role in downregulating the response to type I and type II IFNs, which suggests that the ability of alphaviruses to inhibit Jak/STAT signaling relates to their in vivo virulence potential.
Intestinal permeability and excretion into bile control the arrival of amlodipine into the systemic circulation after oral administration

The objective of this study was to identify the factors controlling the arrival of amlodipine into the systemic circulation after oral administration in the fasting state. Dissolution data were collected with the rotating paddle and the flow‐through apparatus. Caco‐2 cell lines were used to assess the intestinal permeability characteristics. Actual in‐vivo data were collected in 24 fasted healthy subjects after single‐dose administration of the same amlodipine besylate tablet formulation used in the in‐vitro dissolution studies. Regardless of the hydrodynamics, dissolution of amlodipine besylate tablets was rapid and complete in media simulating the contents of the upper gastrointestinal tract in the fasting state. Permeability of amlodipine through Caco‐2 cell lines was lower than propranolol's and higher than ranitidine's, indicating that transport through the intestinal mucosa may be one process that limits the arrival into the systemic circulation. Indeed, the deconvoluted profile indicated that arrival into portal blood occurs at rates much slower than gastric emptying or dissolution rates. However, prediction of amlodipine's mean plasma profile after oral administration became possible only after additionally assuming excretion of amlodipine into the bile and a reasonable gastrointestinal residence time. Interestingly, in‐vitro permeability data collected in this or in previous studies were inappropriate for simulating the mean actual plasma profile.