Miracle-dz/UniFAR-FTUs huggingface dataset:
Left Ventricular Response to Exercise in Regular Runners and Controls: A Radionuclide Evaluation

Radionuclide angiography was performed during upright exercise to compare left ventricular function in nine regular runners to nine age-matched, healthy controls. Heart rate, blood pressure, left ventricular ejection fraction (LVEF), end diastolic volume index (EDVI), end systolic volume index (ESVI), and stroke volume index (SVI) were measured at rest and at 40%, 60%, 80%, and 100% of maximum work capacity (mean maximal workload [KPM ± SD] was 1,773 ± 157 in runners and 1,260 ± 324 in controls). The resting data of runners and controls were similar. There were no significant differences in heart rate, systolic blood pressure, and LVEF between runners and controls during exercise. SVI and EDVI were higher in runners during exercise (P<0.05). ESVI was lower in controls at a 60% level of exercise (P<0.05). The data indicate that an early and sustained increase in the diastolic volume of the left ventricle is important for enhanced cardiac performance of regular runners during exercise
The Effects of Selective History and Environmental Heterogeneity on Inbreeding Depression in Experimental Populations of Drosophila melanogaster

Inbreeding depression varies considerably among populations, but only some aspects of this variation have been thoroughly studied. Because inbreeding depression requires genetic variation, factors that influence the amount of standing variation can affect the magnitude of inbreeding depression. Environmental heterogeneity has long been considered an important contributor to the maintenance of genetic variation, but its effects on inbreeding depression have been largely ignored by empiricists. Here we compare inbreeding depression, measured in two environments, for 20 experimental populations of Drosophila melanogaster that have been maintained under four different selection regimes, including two types of environmentally homogeneous selection and two types environmentally heterogeneous selection. In line with theory, we find considerably higher inbreeding depression in populations from heterogeneous selection regimes. We also use our data set to test whether inbreeding depression is correlated with either stress or the phenotypic coefficient of variation (CV), as suggested by some recent studies. Though both of these factors are significant predictors of inbreeding depression in our study, there is an effect of assay environment on inbreeding depression that cannot be explained by either stress or CV.
GPs' and health visitors' views on the diagnosis and management of postnatal depression: a qualitative study.

BACKGROUND In the UK, 8-15% of women suffer from postnatal depression, with long-term consequences for maternal mood and child development. Previous literature suggests that health visitors struggle with their conflicting roles with respect to mother and infant. Current policy is redirecting the emphasis and organisation of health visitor work, but guidelines state that health visitors and GPs should continue to have a major role in the detection and management of postnatal depression. AIM To explore the views of GPs and health visitors on the diagnosis and management of postnatal depression. DESIGN OF STUDY A qualitative study nested within a multicentre randomised controlled trial. SETTING Nine primary care trusts in Bristol, Manchester, and London. METHOD In-depth interviews with GPs and health visitors from primary care trusts participating in a randomised controlled trial of antidepressants versus health visitor-delivered non-directive counselling. Interviews were audiotaped and fully transcribed. Thematic analysis with an iterative approach was used to develop conceptual categories from the transcripts. RESULTS Nineteen GPs and 14 health visitors were interviewed. GPs and health visitors described their work in making and negotiating the diagnosis of postnatal depression, the value of a long-term relationship with the woman, and how labelling affects management of women with postnatal depression. Responders described how they viewed others' roles in the management of postnatal depression, and how national policy and local organisational changes had an impact on patient care, so that no one health professional was assuming overall responsibility for the care of women with postnatal depression. CONCLUSION Ongoing organisational changes within primary care, such as the implementation of corporate working by health visitors, affect care provided to women after birth, which in turn has an impact on the diagnosis and management of postnatal depression.
Osmotic stress and the cytoskeleton: the R(h)ole of Rho GTPases

Hyperosmotic stress initiates a variety of compensatory and adaptive responses, which either serve to restore near‐normal volume or remodel and reinforce the cell structure to withstand the physical challenge. The latter response is brought about by the reorganization of the cytoskeleton; however, the underlying mechanisms are not well understood. Recent research has provided major breakthroughs in our knowledge about the link between message and structure, i.e. between signalling and cytoskeletal remodelling, predominantly in the context of cell migration. The major components of this progress are the in‐depth characterization of Rho family small GTPases, master regulators of the cytoskeleton, and the discovery of the actin‐related protein 2/3 complex, a signalling‐sensitive structural element of the actin polymerization machinery. The primary aim of this review is to find the place of these novel and crucial players in osmotically induced (volume‐dependent) remodelling of the cytoskeleton. We aim to address three questions: (1) What are the major structural changes in the cytoskeleton under hyperosmotic conditions? (2) Are the Rho family small GTPases (Rho, Rac and Cdc42) regulated by osmotic stress, and if so, by what mechanisms? (3) Are Rho GTPases involved, as mediators, in major adaptive responses, including cytoskeleton rearrangement, changes in ion transport and genetic reprogramming? Our answers will show how fragmentary our current knowledge is in these areas. Therefore, this overview has been written with the hardly disguised intention that it might foster further research in this field by highlighting some intriguing questions.
A diplotype in the lymphotoxin alpha gene is associated with differential expression of LTA mRNA induced by Gram‐positive and Gram‐negative bacteria

We sequenced the lymphotoxin alpha (LTA) promoter and identified LTA10G>A in strong linkage with LTA252G>A and LTA723C>A. Stimulated cells from LTA723AA: LTA252GG:LTA10AA individuals had significantly higher LTA mRNA levels than LTA723CC:LTA252AA:LTA10GG and LTA723AA:LTA252AG:LTA10GA individuals, suggesting that this diplotype may contain a functional polymorphism explaining the observed disease associations with LTA252G>A.
Endothelial cell‐derived bone morphogenetic proteins regulate glial differentiation of cortical progenitors

Gliogenesis is an important component of cortical development during the postnatal period. Two macroglial cells are generated in a particular order, i.e. astrocytes first and oligodendrocytes later. The mechanisms underlying this sequence of glial differentiation are unknown but interactions with blood vessels are postulated to play a role. We show, using a mouse in‐vitro coculture system, that endothelial cells promote astrocyte differentiation but inhibit oligodendrocyte differentiation of postnatal cortical progenitors. Endothelial cells produce bone morphogenetic proteins (BMPs) to activate Sma‐ and Mad‐related protein (Smad) signalling in progenitors and the effects of endothelial cells on glial differentiation are blocked by the BMP antagonist Noggin. Differentiation of progenitors into astrocytes results in the inhibition of endothelial cell growth, accompanied by changes in gene expression of angiogenic factors, indicating bidirectional interactions between progenitors and endothelial cells. In vivo, Smad signalling is activated in various types of cortical cells including progenitors in association with astrogenesis but is inactivated before the peak of oligodendrogenesis. Capillary vessels isolated from the developing cortex express high levels of BMPs. Together, these results demonstrate that endothelial cells regulate glial differentiation by secreting BMPs in vitro and suggest a similar role in cortical gliogenesis in vivo.
Aggravated restenosis and atherogenesis in ApoCIII transgenic mice but lack of protection in ApoCIII knockouts: the effect of authentic triglyceride-rich lipoproteins with and without ApoCIII.

AIM Previously, our group and others have demonstrated a causative relationship between severe hypertriglyceridaemia and atherogenesis in mice. Furthermore, clinical investigations have shown high levels of plasma Apolipoprotein C-III (ApoCIII) associated with hypertriglyceridaemia and even cardiovascular disease. However, it remains unclear whether ApoCIII affects restenosis in vivo, and whether such an effect is mediated by ApoCIII alone, or in combination with hypertriglyceridaemia. We sought to investigate ApoCIII in restenosis and clarify how smooth muscle cells (SMCs) respond to authentic triglyceride-rich lipoproteins (TRLs) with or without ApoCIII (TRLs ± ApoCIII). METHODS AND RESULTS ApoCIII transgenic (ApoCIIItg) and knockout (ApoCIII-/-) mice underwent endothelial denudation to model restenosis. Here, ApoCIIItg mice displayed severe hypertriglyceridaemia and increased neointimal formation compared with wild-type (WT) or ApoCIII-/- mice. Furthermore, increased proliferating cell nuclear antigen (PCNA)-positive cells, Mac-3, and vascular cell adhesion protein-1 (VCAM-1) expression, and 4-hydroxynonenal (4HNE) production were found in lesion sites. ApoCIIItg and ApoCIII-/- mice were then crossed to low-density lipoprotein receptor-deficient (Ldlr-/-) mice and fed an atherogenic diet. ApoCIIItg/Ldlr-/- mice had significantly increased atherosclerotic lesions. However, there was no statistical difference in restenosis between ApoCIII-/- and WT mice, and in atherosclerosis between ApoCIII/Ldlr double knockout and Ldlr-/- mice. SMCs were then incubated in vitro with authentic TRLs ± ApoCIII isolated from extreme hypertriglyceridaemia glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1-deficient (GPIHBP1-/-) mice crossed with ApoCIIItg or ApoCIII-/- mice. It was shown that TRLs + ApoCIII promoted SMC proliferation, VCAM-1 expression, and reactive oxygen species (ROS) production, and activated the Akt pathway. Scavenging ROS significantly reduced SMC activation caused by TRLs + ApoCIII. CONCLUSIONS Severe hypertriglyceridaemia resulting from ApoCIII overexpression promotes restenosis and atherosclerosis. Furthermore, we demonstrated that TRLs + ApoCIII promotes SMC proliferation.
Health-related quality of life among heavy-drinking college students.

OBJECTIVE To examine unique contributions of depression, alcohol consumption, and alcohol-related consequences on functional health outcomes in college students. METHODS Participants were heavy-drinking undergraduate students (N = 207) who completed self-report questionnaires. RESULTS For men and women, depression predicted overall general health and mental health ratings. For women, depression predicted number of days of role limitations due to poor physical or mental health and number of days of not getting enough sleep or rest. CONCLUSIONS Findings suggest that depression may have a more pervasive association with HRQOL than alcohol misuse or alcohol-related consequences in college students.
Time perception impairment following thalamic stroke: A case study

ABSTRACT Impaired time perception is considered to be a relatively unusual and poorly understood consequence of brain injury. This paper presents a case study of altered time perception in JB, a 50-year-old woman who in 2011 had a small thalamic stroke affecting the right anteromedian region. We report on her subjective experience and present results from studies of retrospective timing (i.e., estimating how much time has passed and the clock time) and prospective timing (i.e., producing and reproducing intervals). The results showed that relative to neurologically healthy and brain-injured controls, JB had impaired retrospective timing and impaired prospective time reproduction. However, her prospective time production did not differ significantly from either of the control groups. We interpret this to mean that JB’s essential timing functions are intact, and that rather, her time perception impairment stems from a problem in anterograde memory for time intervals. Further, we argue that unlike other cognitive domains, time perception alteration is neither anticipated nor evaluated in most patients, yet these impairments can have a remarkably serious impact on daily life. We encourage further investigation of this topic.
Exercise-induced expression of heme oxygenase-1 in human lymphocytes

The aim of the present investigation was to determine whether an acute bout of exercise increases heme oxygenase-1 (HO-1) mRNA accumulation in human lymphocytes. Eight male subjects performed separate exercise and rest trials in a randomised order at least 10 days apart. In the exercise trial subjects ran for 75-min at a speed corresponding to 70% maximal oxygen uptake, and in the resting trial subjects sat calmly in the laboratory for an equivalent period of time. Lymphocytes were harvested from blood samples taken before and after each trial. Total RNA was isolated and used to determine the fold-change in HO-1 mRNA accumulation relative to baseline values using real time reverse transcription-polymerase chain reaction. HO-1 protein was determined by Western blotting. Six of the eight subjects showed an increase in HO-1 mRNA greater than two-fold after exercise. The median peak fold-change was 2.7 fold with one subject showing a particularly pronounced response (20-fold) 24 h post-exercise. In the rest trial the level of HO-1 mRNA did not change over the period of investigation. There was also an increase in HO-1 protein 2 h after exercise. These results complement an earlier study showing that acute exercise of a different type (half marathon) leads to an increase in HO-1 expression in lymphocytes.
Dual functions of the Hsm3 protein in chaperoning and scaffolding regulatory particle subunits during the proteasome assembly

The 26S proteasome, a molecular machine responsible for regulated protein degradation, consists of a proteolytic core particle (20S CP) associated with 19S regulatory particles (19S RPs) subdivided into base and lid subcomplexes. The assembly of 19S RP base subcomplex is mediated by multiple dedicated chaperones. Among these, Hsm3 is important for normal growth and directly targets the carboxyl-terminal (C-terminal) domain of Rpt1 of the Rpt1–Rpt2–Rpn1 assembly intermediate. Here, we report crystal structures of the yeast Hsm3 chaperone free and bound to the C-terminal domain of Rpt1. Unexpectedly, the structure of the complex suggests that within the Hsm3–Rpt1–Rpt2 module, Hsm3 also contacts Rpt2. We show that in both yeast and mammals, Hsm3 actually directly binds the AAA domain of Rpt2. The Hsm3 C-terminal region involved in this interaction is required in vivo for base assembly, although it is dispensable for binding Rpt1. Although Rpt1 and Rpt2 exhibit weak affinity for each other, Hsm3 unexpectedly acts as an essential matchmaker for the Rpt1-Rpt2-Rpn1 assembly by bridging both Rpt1 and Rpt2. In addition, we provide structural and biochemical evidence on how Hsm3/S5b may regulate the 19S RP association to the 20S CP proteasome. Our data point out the diverse functions of assembly chaperones.
Helicobacter pylori isolates from proximal and distal stomach of patients never treated and already treated show genetic variability and discordant antibiotic resistance

Introduction The treatment failure of Helicobacter pylori (H. pylori) infection may be mainly because of antibiotic resistance and the presence of a mixed infection in the same patient. Aim To investigate the incidence of mixed infection and discordant antibiotic resistance in patients never treated and already treated. Materials and methods Susceptibility test to amoxicillin, rifabutin, tinidazole, clarithromycin, levofloxacin, and moxifloxacin was conducted on H. pylori strains culture from 76 patients never treated and 72 patients already treated unsuccessfully. DNA fingerprinting was determined on H. pylori strains harboring in the same patient with a discordant resistance to the same antibiotic. Results Forty percent of patients never treated and 53% of patients already treated showed a pangastric infection. The overall resistance to amoxicillin, clarithromycin, and tinidazole was significantly higher in patients with pangastric infection in comparison with those with the infection in the antrum (P<0.05). Discordant resistance was present in 33% of patients never treated, and 21% of patients already treated. DNA fingerprinting showed substantial differences among DNA patterns suggesting a mixed infection. Conclusion Culture and susceptibility test should be performed when necessary not only in the antrum but also in the fundus of patients with H. pylori infection.
Elastic fiber during development and aging

Elastin molecules aggregate in the extracellular space where they are crosslinked by stable desmosine bridges. The resulting polymer is structurally organized as branched fibers and lamellae, which, in skin, are wider (a few microns) in the deep dermis and become progressively thinner (fraction of a micron) towards the papillary dermis. Several general and local factors seem to regulate elastin gene expression, deposition and degradation. In skin, the volume density of the elastin network increases from birth up to maturity, when it accounts for about 3–4% of the tissue. However, its amount and distribution depend on dermis areas, which are different among subjects and change with age. Several matrix molecules (glycosaminoglycans, decorin, biglycan, osteopontin) have been found to be associated with elastin into the normal fiber, and several others have been recognized within pathologic elastic fiber (osteonectin, vitronectin, alkaline phosphatase in PXE). With age, and in some pathologic conditions, skin elastin may undergo irreversible structural and compositional changes, which seem to progress from localized deposition of osmiophilic materials to the substitution of the great majority of the amorphous elastin with interwoven filaments negative for elastin specific antibodies. Microsc. Res. Tech. 38:428–435, 1997. © 1997 Wiley‐Liss, Inc.
Growth, yield and seed composition of native Australian legumes with potential as grain crops.

BACKGROUND Many Australian native legumes grow in arid and nutrient-poor environments. Yet few Australian herbaceous legumes have been investigated for domestication potential. This study compared growth and reproductive traits, grain yield and seed composition of 17 native Australian legumes with three commercial grain legumes. RESULTS Seed yields of seven native legumes were > 40% of Cicer arietnum, with highest seed yields and harvest indices in Glycine sp. (14.4 g per plant, 0.54 g g(-1) ) and Lotus cruentus (10.2 g per plant, 0.65 g g(-1) ). Five native species flowered earlier than field pea (Pisum sativa) (109 days), though many were slower to flower and set seed. Largest seeds were found in Glycine canescens (17 mg), with seed of other native species 14 times smaller than commercial cultivars. Seed composition of many native legumes was similar to commercial cultivars (200-330 g protein kg(-1) dry weight (DW), 130-430 g dietary fibre kg(-1) DW). Two Cullen species had high fat content (>110 g kg(-1) DW) and Trigonella sauvissima had the highest crude protein content (370 g kg(-1) DW). CONCLUSION The seed composition and reproductive traits of some wild native Australian legumes suggest they could offer potential as grain crops for soils and environments where the current grain legumes are uneconomic. Further evaluation of genetic diversity, especially for seed size, overall productivity, and reproductive development is needed.
Bacterial exotoxins downregulate cathelicidin (hCAP‐18/LL‐37) and human β‐defensin 1 (HBD‐1) expression in the intestinal epithelial cells

Cathelicidin (hCAP‐18/LL‐37) and β‐defensin 1 (HBD‐1) are human antimicrobial peptides (AMPs) with high basal expression levels, which form the first line of host defence against infections over the epithelial surfaces. The antimicrobial functions owe to their direct microbicidal effects as well as the immunomodulatory role. Pathogenic microorganisms have developed multiple modalities including transcriptional repression to combat this arm of the host immune response. The precise mechanisms and the pathogen‐derived molecules responsible for transcriptional downregulation remain unknown. Here, we have shown that enteric pathogens suppress LL‐37 and HBD‐1 expression in the intestinal epithelial cells (IECs) with Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) exerting the most dramatic effects. Cholera toxin (CT) and labile toxin (LT), the major virulence proteins of V. cholerae and ETEC, respectively, are predominantly responsible for these effects, both in vitro and in vivo. CT transcriptionally downregulates the AMPs by activating several intracellular signalling pathways involving protein kinase A (PKA), ERK MAPKinase and Cox‐2 downstream of cAMP accumulation and inducible cAMP early repressor (ICER) may mediate this role of CT, at least in part. This is the first report to show transcriptional repression of the AMPs through the activation of cellular signal transduction pathways by well‐known virulence proteins of pathogenic microorganisms.
High interleukin‐6 plasma levels are associated with functional impairment in older patients with Vascular dementia

In older individuals, inflammatory mechanisms have been linked to the pathogenesis of both dementia and functional impairment. In this cross‐sectional study we have investigated the possible association between some markers of systemic inflammation and functional status, in a sample of one hundred and forty older demented patients including 60 patients with late onset Alzheimer's disease (LOAD) and 80 with vascular dementia (VD). Functional status was evaluated by Barthel Index (BI); the total score ranged from 0 (total dependency) to 20 (total autonomy). Interleukin‐1β, Tumor Necrosis Factor‐α, Interleukin‐ 6, Interleukin‐ 8, and Transforming Grow Factor β were quantified by ELISA. Among the cytokines evaluated, only IL‐6 was correlated with the BI (r: −0.32, p < 0.001). The mean levels of IL‐6 progressively decreased from I (9.50 pg/mL), to II (6.40 pg/mL), to III BI tertile (4.80 pg/mL) (p < 0.02).