Miracle-dz/UniFAR-FTUs huggingface dataset:
Folded, concatenated genomes as replication intermediates of bacteriophage T7 DNA

A complex form of bacteriophage T7 DNA, containing up to several hundred phage equivalents of DNA, arises during replication of T7. The complex was stable to treatment with ionic detergent, Pronase, and phenol. The complex form normally exists for only a short time, corresponding to the phase of rapid T7 DNA synthesis. It is then converted to shorter molecules, both concatemers and unit-size DNA. The complex was stable up to the temperature of denaturation of the bihelix. It consisted of a series of loops amanating from a dense central core, as shownby electron microscopy. The complex form is similar to the relaxed Escherichia coli folded chromosome ('nucleoid'). The loops contained an average of 0.7 to 0.8 phage equivalent of DNA. During infection by phage with an amber mutation in gene 3 (endonuclease), formation of the complex occurred normally, but its maturation to unit-size DNA blocked. Before treatment with phenol, the complex contained short fragments of newly replicated DNA. These were released as single-stranded pieces during phenol treatment. A pathway for T7 DNA replication is indicated in which the flow of material is from unit-size DNA to linear concatemers to the complex form, and then back to unit-size DNA by way of linear concatemers.
TRANSCRIPTIONAL REGULATION OF INTERLEKIN 2 IN SLE T CELLS

Interleukin-2 (IL-2) is a central cytokine required for the activation of T, B, and NK cells. It propagates the immune response and terminates it by promoting the activation induced cell death of T cells. IL-2 production is altered in T cells of patients with systemic lupus erythematosus (SLE). The consequence of reduced IL-2 production in SLE is decreased immune response to infectious agents. Decreased IL-2 production by SLE T cells is the result of transcriptional repression of the IL-2 gene. This article will review the defective transcription regulation of IL-2 in SLE T cells, which is the result of decreased expression of the enhancers NF-κB and AP1 and the increased expression of the transcriptional repressor CREM.
The cost effectiveness of zoledronic acid 5 mg for the management of postmenopausal osteoporosis in women with prior fractures: evidence from Finland, Norway and the Netherlands

Abstract Objective: This study was conducted to assess the cost effectiveness of zoledronic acid 5 mg as a first-line treatment for the secondary prevention of fragility fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands. Methods: A discrete-event, individual-patient computer-simulation model was used to compare the cost effectiveness of zoledronic acid with that of basic treatment (calcium and vitamin D) and commonly prescribed bisphosphonates in postmenopausal women aged 50–80 years who have experienced one previous fracture and have a bone mineral density T-score of −2.5. Results: The cost per quality-adjusted life-year (QALY) gained with zoledronic acid compared with basic treatment ranged from being cost saving in all age groups in Norway, to costing approximately €19,000 in Finland and €22,300 in the Netherlands. Compared with the other branded bisphosphonates, zoledronic acid was cost saving in many scenarios, including all age groups in Finland. In Norway, zoledronic acid dominated branded risedronate and ibandronate in all age groups and dominated or had incremental cost-effectiveness ratios (ICERs) of up to NOK83,954 per QALY gained compared with branded alendronate. In the Netherlands, zoledronic acid dominated branded intravenous ibandronate in all age groups; compared with branded risedronate and oral ibandronate, zoledronic acid dominated or had ICERs of up to €4832 per QALY gained; compared with branded alendronate, it had ICERs of up to €48,383 per QALY gained. In all three countries, zoledronic acid may be cost effective compared with generic alendronate when patient compliance with drug therapy is taken into account. Sensitivity analyses showed that the model was robust to changes in key values. The main model limitations were the lack of real-life compliance and persistence data, and lack of country-specific data for some parameters. Conclusions: Using local or commonly used thresholds, this analysis suggests that zoledronic acid would be a cost-effective first-line option compared with other branded bisphosphonates and, in some scenarios, compared with generic alendronate, for the secondary prevention of fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands.
Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood-Stage Plasmodium falciparum Infection

The human complement system is the frontline defense mechanism against invading pathogens. The coexistence of humans and microbes throughout evolution has produced ingenious molecular mechanisms by which microorganisms escape complement attack. A common evasion strategy used by diverse pathogens is the hijacking of soluble human complement regulators to their surfaces to afford protection from complement activation. One such host regulator is factor H (FH), which acts as a negative regulator of complement to protect host tissues from aberrant complement activation. In this report, we show that Plasmodium falciparum merozoites, the invasive form of the malaria parasites, actively recruit FH and its alternative spliced form FH-like protein 1 when exposed to human serum. We have mapped the binding site in FH that recognizes merozoites and identified Pf92, a member of the six-cysteine family of Plasmodium surface proteins, as its direct interaction partner. When bound to merozoites, FH retains cofactor activity, a key function that allows it to downregulate the alternative pathway of complement. In P. falciparum parasites that lack Pf92, we observed changes in the pattern of C3b cleavage that are consistent with decreased regulation of complement activation. These results also show that recruitment of FH affords P. falciparum merozoites protection from complement-mediated lysis. Our study provides new insights on mechanisms of immune evasion of malaria parasites and highlights the important function of surface coat proteins in the interplay between complement regulation and successful infection of the host.
Advances in Ophthalmic Techniques and Technology: What should I note when assessing the retinal vasculature?

The retinal vasculature is unique in that, unlike any other systemic vascular bed, it can be assessed directly and non-invasively in vivo. Optometrists routinely evaluate the state of the retina and its microvasculature as part of any normal ophthalmic assessment and if considered carefully, such an evaluation has the potential to provide a unique insight into general vascular health. Advances in imaging technology have enhanced our ability to evaluate and document changes in the retinal vasculature over time and the recent introduction of new objective retinal image analysis techniques has the potential to significantly improve the accuracy and usability of quantifiable retinal vessel parameters such as calibre, arteriovenous ratio (AV ratio) and vessel tortuosity. This article will aim to outline the relevant anatomy and physiology of the retinal vasculature and go on to summarise the current evidence linking alterations in the retinal microvasculature to the occurrence of ocular and systemic vascular disease, with reference to the recent developments in imaging technology that are aiding our ability to make these links now and into the future.
Prevalence of Abnormal Urodynamic Test Results in Continent Women With Severe Genitourinary Prolapse

Twenty-two clinically continent women with severe genitourinary prolapse were evaluated urodynamically to determine the prevalence of urodynamic abnormalities that could lead to potential urinary incontinence. Urodynamic testing found an occult incontinence disorder in 13 women (59%), of whom four had urine loss during cough pressure profiles after pessary placement, four had uninhibited detrusor contractions during retrograde medium-fill water cystometry, and five had both stress urinary incontinence and an unstable bladder. Therefore, nine of the 22 patients (41%) had uninhibited detrusor contractions during urodynamic testing. However, uroflowmetry did not reveal voiding dysfunction in this group, although peak flow rates appeared to be lower in the subgroup of women manifesting uninhibited detrusor contractions. Associated symptoms of frequency, nocturia, and urgency occurred in 41% of the women in this study; four of nine (44%) who had normal urodynamic test results, five of 13 (38%) who had abnormal test results, and five of nine (56%) who had an unstable bladder. Therefore, associated symptoms could not be used to determine which women would have abnormal urodynamic test results. These preliminary results suggest that women with genitourinary prolapse may be at risk for an occult incontinence disorder that is masked by the prolapse and that could manifest after corrective surgery for prolapse. Urodynamic testing is suggested for women with genitourinary prolapse who present with or without symptoms of incontinence, so that more data can be obtained to determine the importance of abnormal test results.
CSF neurofilament levels: A potential prognostic marker in Guillain–Barré syndrome

Long-term morbidity from Guillain–Barré syndrome (GBS) is caused by axonal damage. This prospective study demonstrated that neurofilaments (NfHs), a biomarker for axonal damage, were of prognostic value in GBS. CSF NfH levels correlated with the F score and Medical Research Council summed score and were higher in patients with neurophysiologic evidence of axonal degeneration compared to those without. Pathologically high CSF NfH levels (>0.73 ng/mL) predicted worse motor and functional outcome.
The Influence of Religiosity on Violent Behavior of Adolescents

Different criminological theories assume that religiosity protects against violent behavior. Up to now, this assumption is tested empirically almost exclusively for the Christian religiosity. The study presented here questions whether such a relationship between religiosity and violent behavior could be found for Muslims, likewise. Using a German-wide representative school survey of 16,545 male students in the ninth grade, who belong either to a Christian or an Islamic denomination, it can be revealed that only for Christians a higher religiosity correlates with a lower rate of violent behavior. This influence of Christian religiosity can be explained by mainly control theory variables. For Muslims, there is no significant correlation between religiosity and violent behavior in a bivariate analysis. A multivariate analysis, however, reveals a suppression effect: Controlling for alcohol consumption, Muslim religiosity increases violent behavior. In addition, high religious Muslims agree more often to norms of masculinity and consume more often media violence, which are risk factors of violent behavior. Accordingly, it can be concluded that religiosity is not a violence-protecting factor in general; instead, a more differentiated view for separate religious groups is necessary.
Role of Afferents in the Differentiation of Bipolar Cells in the Mouse Retina

To establish dendritic arbors that integrate properly into a neural circuit, neurons must rely on cues from the local environment. The neurons presynaptic to these arbors, the afferents, are one potential source of these cues, but the particular dendritic features they regulate remain unclear. Retinal bipolar cells can be classified by the type of photoreceptor, cone or rod, forming synaptic contacts with their dendrites, suggesting a potential role of these afferents in shaping the bipolar cell dendritic arbor. In the present investigation, the role of photoreceptors in directing the differentiation of bipolar cells has been studied using two genetically modified “coneless” and “conefull” mice. Single cone (Type 7/CB4a) and rod bipolar cells were labeled with DiI to reveal the entire dendritic arbor and subsequently analyzed for several morphological features. For both cone and rod bipolar cells, the dendritic field area, number of dendritic terminals, and stratification of terminals in the outer plexiform layer were comparable among coneless, conefull, and wild-type retinas, and the overall morphological appearance of each type of cell was essentially conserved, indicating an independence from afferent specification. The presence of normal afferents was, however, found to be critical for the proper spatial distribution of dendritic terminals, exhibiting a clustered distribution for the cone bipolar cells and a dispersed distribution for the rod bipolar cells. These results demonstrate a selectivity in the afferent dependency of bipolar cell differentiation, their basic morphogenetic plan commanded cell intrinsically, and their fine terminal connectivity directed by the afferents themselves.
Mitochondrial diazepam-binding inhibitor receptor complex agonists antagonize dizocilpine amnesia: putative role for allopregnanolone.

In rats trained to retain a passive avoidance response or to retrieve a learned task in the radial and water maze tests, a pretreatment with 2-hexyl-3-indoleacetamide (FGIN-1-27) (IC50 57 mumol/kg p.o.) or 4' chlorodiazepam (4'CD) (15 mumol/kg i.p.), two steroidogenic ligands at the mitochondria diazepam-binding inhibitor receptor complex (MDRC), antagonized the performance deficit elicited by dizocilpine (0.3 mumol/kg i.p.), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. The 1-(2-chlorophenyl)-N-methyl-N-(-1-methyl-propyl)-3-isoquinoline carboxamide (PK-11195), an antagonist at MDRC in vivo, failed to modify the disruptive effect of dizocilpine in the passive avoidance response but reversed the FGIN-1-27- or 4' CD-induced antagonism of dizocilpine behavioral actions. Pretreatment with pregnenolone sulfate (48 mumol/kg i.p.), 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (THDOC) (15 mumol/kg i.v.) and 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) (15 mumol/kg i.v.) also reduced the passive avoidance retention deficit elicited by dizocilpine. The (17-beta)-17-[[bis(1-methylethyl)amino[carbonyl]androstane-3,5-diene-3- carboxylic acid (SKF-105111), a 5 alpha-reductase inhibitor, blocked the antagonism of dizocilpine behavioral actions by pregnenolone sulfate or by FGIN-1-27 but not those caused by THDOC or allopregnanolone either in normal or adrenalectomized-castrated rats. Thus, it is inferred that the amnesic effect of dizocilpine is counteracted by FGIN-1-27, 4'CD and pregnenolone sulfate because of their ability to increase brain accumulation of allopregnanolone.
Purification of Ovine Respiratory Complex I Results in a Highly Active and Stable Preparation*

NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies.
Drivers of protogynous sex change differ across spatial scales

The influence of social demography on sex change schedules in protogynous reef fishes is well established, yet effects across spatial scales (in particular, the magnitude of natural variation relative to size-selective fishing effects) are poorly understood. Here, I examine variation in timing of sex change for exploited parrotfishes across a range of environmental, anthropogenic and geographical factors. Results were highly dependent on spatial scale. Fishing pressure was the most influential factor determining length at sex change at the within-island scale where a wide range of anthropogenic pressure existed. Sex transition occurred at smaller sizes where fishing pressure was high. Among islands, however, differences were overwhelmingly predicted by reefal-scale structural features, a pattern evident for all species examined. For the most abundant species, Chlorurus spilurus, length at sex change increased at higher overall densities and greater female-to-male sex ratios at all islands except where targeted by fishermen; here the trend was reversed. This implies differing selective pressures on adult individuals can significantly alter sex change dynamics, highlighting the importance of social structure, demography and the selective forces structuring populations. Considerable life-history responses to exploitation were observed, but results suggest potential fishing effects on demography may be obscured by natural variation at biogeographic scales.
Neurochemical and Immunocytochemical Studies on the Distribution of N‐Acetyl‐Aspartylglutamate and N‐Acetyl‐Aspartate in Rat Spinal Cord and Some Peripheral Nervous Tissues

Abstract: HPLC analysis of rat spinal cord revealed a uniform distribution of N‐acetyl‐aspartate (NAA) across both longitudinal and dorsoventral axes. In contrast, ventral cord N‐acetyl‐aspartylglutamate (NAAG) levels were significantly higher than those measured in dorsal halves of cervical, thoracic, and lumbar segments. Immunocytochemical studies using an affinity‐purified antiserum raised against NAAG‐bovine serum albumin revealed an intense staining of motoneurons within rat spinal cord. Along with the considerable NAAG content in ventral roots, these results suggest that NAAG may be concentrated in motoneurons and play a role in motor pathways. NAAG was also present in other peripheral neural tissues, including dorsal roots, dorsal root ganglia, superior cervical ganglia, and sciatic nerve. It is interesting that NAA levels in peripheral nervous tissues were lower than those in CNS structures and that NAA levels in ventral roots and sciatic nerve were lower than NAAG levels. These findings further document a lack of correlation between NAAG and NAA levels in both central and peripheral nervous tissues. Taken together, these data demonstrate the presence of NAAG in nonglutamatergic neuronal systems and suggest a more complex role of NAAG in neuronal physiology than previously postulated.
Impact of somatostatin analogs on the heart in acromegaly: a metaanalysis.

CONTEXT Acromegaly can be complicated by cardiomyopathy. Treatment with somatostatin analogs has been shown to improve some cardiac parameters, but most published clinical trials involved few patients and were not randomized or controlled. In addition, their results are rather variable. OBJECTIVE The objective of the study was to conduct a metaanalysis aimed at obtaining a more accurate picture of the effect of somatostatin analogs on the heart in patients with acromegaly. DESIGN We systematically reviewed all studies of somatostatin analogs in acromegaly. Eighteen studies were identified in three databases. We conducted a combined analysis of the effects of somatostatin analogs by using the overall effect size to evaluate significance and by computing the weighted mean differences with and without treatment to assess the effect size. RESULTS Somatostatin analog treatment was associated with significant reductions in the heart rate [-5.8 (2.1) beats/min], the left ventricular mass index [-22.3 (6.7) g/m(2)], interventricular septum thickness [-0.3 (0.2) mm], left ventricular posterior wall thickness [-0.8 (0.4) mm], and the ratio of the E-wave and A-wave peak velocities of the mitral flow profile [0.2 (0.1)]. It was also associated with improved exercise tolerance [1.6 (0.4) min]. Trends toward beneficial effects were noted for the left ventricular end-diastolic dimension [-1.5 (2.2) mm] and the left ventricular ejection fraction [3.3% (1.7%)]. Overall effect sizes were not significant for blood pressure, left ventricular end-systolic dimension, or fractional shortening. Bigger improvements were observed in studies with larger falls in IGF-I and/or GH levels and studies of younger patients. CONCLUSION This metaanalysis confirms that somatostatin analog therapy aimed at achieving stringent control of serum GH/IGF-I concentrations in patients with acromegaly is associated with significant positive effects on morphological and functional hemodynamic parameters.
INFLUENCE OF DIETARY SELENIUM SOURCES ON THYROID HORMONE ACTIVATION, TISSUE SELENIUM DISTRIBUTION AND ANTIOXIDANT ENZYMES STATUS IN BROILER CHICKENS

on thyroid hormone activation, tissue Se distribution and antioxidant enzymes status in broiler chickens. A total of 320 one-day old broiler chicks were randomly attributed to 5 experimental groups and fed iso-energetic and isonitrogenous diets. The basal diet was supplemented with 0 (control) or 0.3 mg/kg Se from sodium selenite (SS), selenomethionine (SM), selenized yeast (SY) or nano elemental selenium (NS). Dietary SY supplementation at 0.3 mg/kg improved both growth performance and feed efficiency compared with the other groups (P 0.05) among treatments. At the end of the test, thioredoxin reductase (TR) and glutathione peroxidase (GPX) activities and also Se concentrations in plasma, liver and breast muscle were greater in groups fed Se-supplemented diets, regardless of source, than in those fed the control diet. The highest values in plasma and tissue Se content were measured in the group supplemented with SY, while the groups receiving NS showed the greatest (P<0.01) plasma and tissues GPX activities. Furthermore, dietary selenium supplementation promoted conversion of thyroxine (T4) to triiodothyronine (T3), which consequently resulted in significantly (P<0.01) higher plasma T3 concentration (p<0.01), while serum thyroxine was not significantly influenced by selenium supplementation. It could be concluded that supplementation of Se can improve antioxidative status and Se concentration in blood and tissues of broiler chick. The dietary supplementation of SY and NS could be utilized more effectively when compared to other Se sources.