Miracle-dz/UniFAR-FTUs huggingface dataset:
Proinsulin Disulfide Maturation and Misfolding in the Endoplasmic Reticulum*

Upon nonreducing Tris-Tricine-urea-SDS-PAGE, newly synthesized proinsulin from pancreatic islets of normal rodents forms a band fast mobility representing the native disulfide isomer, which is efficiently secreted. In addition at least two slower migrating “isomer 1 and 2” bands are recovered, not discernible under reducing conditions, which represent minor species that exhibit less efficient secretion. Although rats and mice have two proinsulin genes, three distinct migrating species are also produced upon proinsulin expression from a single wild-type human proinsulin cDNA. The “Akita-type” proinsulin mutation, which causes dominant-negative diabetes mellitus due to point mutation C(A7)Y that leaves B7-cysteine without its disulfide pairing partner, is recovered as a form that near quantitatively co-migrates with the aberrant isomer 1 band of proinsulin. Anomalous migration is also demonstrated for several other mutants lacking a single cysteine. In islets from PERK–/– mice, which exhibit premature loss of pancreatic beta cells, hypersynthesis of proinsulin increases the amount of nonnative proinsulin isomers. Such findings appear consistent with an hypothesis that supranormal production of nonnative proinsulin may predispose to pancreatic beta cell toxicity.
Analysis of the termini of the DNA of bovine parvovirus: demonstration of sequence inversion at the left terminus and its implication for the replication model

The distribution of terminal-sequence orientations in the viral DNA of bovine parvovirus (BPV), an autonomous parvovirus, was studied by end labeling and restriction enzyme digestion and also by cloning. The left (3') end of the minus strand of BPV was found in two alternative sequence orientations (designated as flip and flop, which are reverse complements of each other), with a 10-fold excess of flip. This is in contrast to the autonomous rodent parvoviruses which encapsidate minus-strand DNA with only the flip orientation at this end. The right (5') end of the minus strand of BPV contained both sequence orientations with equal frequencies, as in the rodent parvoviruses. Sequence inversions were also detected at both ends of the plus strand, which makes up about 10% of the encapsidated BPV DNA. Each terminus of BPV DNA had a characteristic ratio of flip to flop forms, and this ratio was restored in the progeny DNA resulting from transfection with genomic clones of different defined terminal conformations. Replicative-form DNA showed the same distribution of terminal-sequence orientations as the reannealed plus and minus virion DNAs, suggesting that the distribution of flip and flop forms observed in virion DNA is not due to selective encapsidation, but rather to the specific distribution of replicative forms. The current replication model for autonomous parvoviruses, which was based on the available data for the rodent parvoviruses, cannot account for the observed distribution of BPV DNA. An alternative model is suggested.
Cell-density-dependent killing of Myxococcus xanthus by autocide AMV

Autocide AMV of Myxococcus xanthus was purified and identified as phosphatidylethanolamine. Alkaline hydrolysis of AMV yielded a high proportion of mono- and diunsaturated fatty acids. The bactericidal activity of AMV on M. xanthus depended upon the density of target cells: the greater the cell density, the greater the killing by AMV. For example, at 2 U of AMV per ml, 0, 50, and 99% killing was measured with 2 X 10(4), 2 X 10(5), and 2 X 10(7) target cells per ml, respectively. The cell-density-dependent activity of AMV was also observed on solid medium. Studies with model lipid compounds suggest that the inhibitory activity of AMV is due to the fatty acid moiety, released from phosphatidylethanolamine by the concerted (enzymatic) activity of many cells. Mutants of M. xanthus selected for resistance to AMI (a mixture of fatty acids) were also resistant to AMV. The possible role of AMV in developmental lysis is discussed.
Newer Findings on a Unified Perspective of Copper Restriction and Cardiomyopathy 1

Abstract The cuproenzymes lysyl oxidase, cytochrome-c oxidase, and superoxide dismutase are key factors in understanding the cardiac hypertrophy and cardiomyopathy associated with dietary copper restriction. The role of copper in cardiac lipid and energy metabolism as a consequence of changes in some of these enzyme activities in comparison with what is known about normal cardiac substrate utilization is discussed here. While the decrease in the nuclear encoded subunits of cytochrome-c oxidase in hearts from copper-deficient rats is known, new evidence suggests that other factors, such as ATP synthase metabolism may be exerting an influence upon this observation. While this review focuses on newer knowledge about energy and fatty acid metabolism in copper deficiency, the extracellular matrix is considered as well. This complex interplay of extracellular and cellular events in copper restriction is outlined as a model for further studies of this unique model of concentric hypertrophy.
How Glomerular Extracapillary Proliferation Might Lead to Loss of Renal Function: Light Microscopic and Immunohistochemical Investigation

Although there has been extensive research into the mechanisms involved in glomerular crescent formation, it is not yet fully understood how this change may cause renal function impairment. The aim of this study is to identify morphologic changes which may be responsible for this phenomenon. Thirty-eight renal biopsies showing glomerulonephritis with extracapillary proliferation (20 vasculitis-related, 6 idiopathic, 9 due to immune-complex deposition and 3 superimposed on diabetic nephropathy) were considered, and 146 glomeruli in which both crescents and the urinary pole were found at the same time, were studied. The involvement of the urinary pole by cellular crescents was observed in 93.1 and 100% of the glomeruli with segmental or circumferential crescents, respectively. A tridimensional study, for the evaluation of the glomeruli as a whole, was performed on 8 biopsies by means of the step-section technique and disclosed the involvement of the urinary space and a close contact between crescent and tubular cells in all 54 investigated glomeruli. The reported features do not seem to be related to the type of cells which formed the crescent. Indeed, as shown by immunohistochemical study on 10 cases with anti-cytokeratin and anti-CD68 antisera, the crescent localization at the urinary pole had no correlation with the prevalence of epithelial or macrophagic cells. These findings suggest that crescents, due to epithelial proliferation or macrophage clustering, tend to localize at the urinary pole and thus come into close contact with cells of the proximal convoluted tubule: the formation of a sort of plug or a ‘glomerular stone’ could well explain the block in the urine flow and the consequent impairment of renal function in the acute phase of the disease, even in those cases where crescents are segmental.
Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes

Objective:To investigate the potential to induce additional cytotoxic T-lymphocyte (CTL) immunity during chronic HIV-1 infection. Design:We selected infrequently targeted or subdominant but conserved HLA-A*0201-binding epitopes in Gag, Pol, Env, Vpu and Vif. These relatively immune silent epitopes were modified as anchor-optimized peptides to improve immunogenicity and delivered on autologous monocyte-derived dendritic cells (MDDCs). Methods:Twelve treatment-naïve HLA-A*0201 HIV-1-infected Danish individuals received 1 × 107 MDDCs subcutaneously (s.c.) (weeks 0, 2, 4 and 8), pulsed with seven CD8+ T-cell epitopes and three CD4+ T-cell epitopes. Epitope-specific responses were evaluated by intracellular cytokine staining for interferon-γ, tumor necrosis factor α and interleukin-2 and/or pentamer labeling 3 weeks prior to, 10 weeks after and 32 weeks after the first immunization. Results:Previously undetected T-cell responses specific for one or more epitopes were induced in all 12 individuals. Half of the participants had sustained CD4+ T-cell responses 32 weeks after immunization. No severe adverse effects were observed. No overall or sustained change in viral load or CD4+ T-cell counts was observed. Conclusion:These data show that it is possible to generate new T-cell responses in treatment-naive HIV-1-infected individuals despite high viral loads, and thereby redirect immunity to target new multiple and rationally selected subdominant CTL epitopes. Further optimization could lead to stronger and more durable cellular responses to selected epitopes with the potential to control viral replication and prevent disease in HIV-1-infected individuals.
Overview of hydrogel-based strategies for application in cardiac tissue regeneration

Cardiovascular diseases remain the leading cause of death globally. Since the adult heart lacks the capacity to regenerate, loss of myocardium following myocardial infarction is irreversible and ultimately leads to failure to maintain cardiac function. In order to repopulate the areas of cell loss in the damaged hearts for restoration of cardiac function, cell transplantation/replacement has been extensively investigated. Recently, biomaterials have emerged as an approach to improve delivery and viability of cells for the regeneration of the damaged heart. Here we review the most common approaches in hydrogel-based cardiac tissue regeneration with particular focus on the implementation of hydrogels to improve cell delivery.
Development and Use of Quality of Care Indicators for Obstetric Care in Women with Preeclampsia, Severe Preeclampsia, and Severe Morbidity

Objective: To develop indicators for evaluating the quality of care in managing preeclampsia. Methods: An expert group helped to develop and validate the following indicators for evaluating quality of care: availability of intensive care; completeness of laboratory tests; appropriateness of drug treatment at admission and before delivery (antihypertensive drugs, anticonvulsants, and dexamethasone); gestational age at which pregnancy should be interrupted; and type of delivery. By using these indicators, it was possible to evaluate the quality of care in 432 patients with preeclampsia. Results: A significant percentage of patients with preeclampsia and “near misses” received low quality of care, regardless of disease severity. Conclusion: A number of interventions are needed to increase the quality of care to help avert maternal deaths in patients with preeclampsia.
Yeast Rmi1/Nce4 Controls Genome Stability as a Subunit of the Sgs1-Top3 Complex

ABSTRACT Genome stability requires a set of RecQ-Top3 DNA helicase-topoisomerase complexes whose sole budding yeast homolog is encoded by SGS1-TOP3. RMI1/NCE4 was identified as a potential intermediate in the SGS1-TOP3 pathway, based on the observation that strains lacking any one of these genes require MUS81 and MMS4 for viability. This idea was tested by confirming that sgs1 and rmi1 mutants display the same spectrum of synthetic lethal interactions, including the requirements for SLX1, SLX4, SLX5, and SLX8, and by demonstrating that rmi1 mus81 synthetic lethality is dependent on homologous recombination. On their own, mutations in RMI1 result in phenotypes that mimic those of sgs1 or top3 strains including slow growth, hyperrecombination, DNA damage sensitivity, and reduced sporulation. And like top3 strains, most rmi1 phenotypes are suppressed by mutations in SGS1. We show that Rmi1 forms a heteromeric complex with Sgs1-Top3 in yeast and that these proteins interact directly in a recombinant system. The Rmi1-Top3 complex is stable in the absence of the Sgs1 helicase, but the loss of either Rmi1 or Top3 in yeast compromises its partner's interaction with Sgs1. Biochemical studies demonstrate that recombinant Rmi1 is a structure-specific DNA binding protein with a preference for cruciform structures. We propose that the DNA binding specificity of Rmi1 plays a role in targeting Sgs1-Top3 to appropriate substrates.
Regional and developmental variations of blood vessel morphometry in the chick embryo chorioallantoic membrane

SUMMARY Avian eggs contain all the necessary materials for embryonic development except for oxygen, which diffuses in from the environment via pores in the hard, calcified eggshell to the chorioallantoic membrane (CAM), the respiratory organ, which is rich in blood vessels. An air cell is formed at the blunt pole of the egg between the two membranes of the eggshell and enlarges during incubation due to water vapor loss. In this study of the CAM of chicken eggs, we compared blood vessel numerical density [NA(v)], area fraction of blood vessels [AA(v)], CAM thickness (DCAM), total length of blood vessels (L) and surface area of the CAM attached to the eggshell (CAMre) with those under the air cell (CAMac) during incubation. We found that NA(v), AA(v), DCAM and L of the CAM increase with embryonic age and development. The NA(v), AA(v) and L under the air cell were higher in relation to the rest of the CAM at all ages tested, while the DCAM under the air cell was always lower than around the rest of the egg. Since the eggshell over the air cell has a relatively greater porosity, and the respiratory gas exchange ratio there is higher than at other areas of the egg, there is a correlation between all the above morphometric data and the eggshell porosity. This suggests optimization of embryonic gas exchange in the chicken egg. We would like to propose that, during natural incubation, an increased gas diffusion under the air cell, together with increased blood vessel numerical density, may compensate for covering of the central part of the eggshell by the incubating parent.
Comparing Male and Female Juveniles Charged With Homicide

This study examines a sample of 136 male and female juveniles charged with attempted homicide or homicide. The purpose of this study is to explore the differences between nondirect file male and female juvenile homicide offenders regarding individual, family, and crime circumstances. Findings suggest that compared to male juvenile offenders, female juvenile homicide offenders have higher rates of reported childhood abuse, more serious substance abuse, and mental health problems including suicidal ideations, depression, anxiety, anger, and irritability. Male juvenile homicide offenders reported higher rates of substance use than their female counterparts but the females had more serious substance abuse problems. Female juveniles were found to more often kill a person known to them and male homicide offenders were found to more often kill a stranger. These findings suggest strongly that male and female juvenile homicide offenders are dissimilar and require unique assessment and treatment.
Assessing fertility in women of advanced reproductive age.

Reproductive capacity in women declines dramatically beyond the fourth decade of life. Oocyte quality seems to be the primary determinant of reproductive potential, although age-related uterine changes may also contribute. Underlying reasons for reproductive decline in women remain unclear, and both ovarian and neuroendocrine mechanisms have been proposed.A number of age-related endocrinologic changes precede menopause and predict diminished reproductive capacity. Thus, "ovarian reserve" screening may identify patients in whom attempts at conventional assisted reproduction is warranted before proceeding with ovum donation. Techniques to preserve the maternal genetic contribution to offspring (in lieu of egg donation), including germinal vesicle transfer and donor ooplasm, are under investigation.
[Food insecurity among Californian Latinos: focus-group observations].

OBJECTIVE To assess the perception and experience with food insecurity among Latinos living in California, as well as their interpretation of the items included in the Food Security Scale. MATERIAL AND METHODS A series of four focus groups were carried out among 30 adults of Latin-American descent living in California. The participant's responses were coded by two researchers to identify the main issues, and to compare them for assessing their convergence. RESULTS The items were well understood and were not perceived as offensive. The conceptual framework was confirmed as a "managed process" with different severity levels. The causes of food insecurity were: unemployment, high cost of some food items, and lack of nutritional information. The demand for nutritional education was constant. CONCLUSION Interpreting data on food insecurity in Latinos requires proper consideration of their particular perceptions.
Morphometric characterisation of rocky reef using multibeam acoustic bathymetric data

Physical parameters of the seabed can be automatically classified using terrestrial landscape morphometric tools. This case study demonstrates the classification of multibeam acoustic data into six ecologically relevant classes in a marine park off the coast of Western Australia. The results of this application, improve the access to fine scale reef characteristics which helps to develop better management strategies for ben-thic habitats. This new morphometric classification method is compared with traditional qualitative feature identification.
Contributions Made by Women Entrepreneurs in Augmenting Socio-Regional-Economic Growth of Emerging Market Economy

Women entrepreneurs have played significant role in the worldwide pursuit for sustained economic development and social progress. Despite all the hurdles, women stood tall and are applauded for their achievements in their respective field. In this context the current study was taken up to (1) review the relevance of women entrepreneurship, (2) examine the contribution made by the women entrepreneurs` in the social and regional development and (3) explore the role played by the women entrepreneurs` in economic development. The aim was to investigate the working of eighteen women entrepreneurs working in Uttar Pradesh, the most populous state of the Republic of India, who have provided employment to hundreds of illiterate, un-skilled, unemployable and under privileged women living in poverty conditions in their local community. The objective was to analyze their contribution towards the society, region and economy. It will also motivate and inspire others to replicate such businesses in their regions. The study aims to provide useful insights to the potential entrepreneurs, policy makers and other stakeholders to evolve mechanism to promote employment generation, poverty alleviation, and socio-economic empowerment at the grass root level, to stimulate inclusive growth.
In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against Macrolide-Resistant and -Susceptible Mycoplasma genitalium Strains

ABSTRACT Mycoplasma genitalium has become well established as an etiological agent of sexually transmitted infections, but due to its fastidious growth requirements, only a few M. genitalium strains are available to determine the MICs of currently used and new antimicrobial agents. Recent clinical trials have suggested that treatment with azithromycin has decreasing efficacy due to an increasing prevalence of macrolide resistance, and alternative treatment with moxifloxacin is similarly under pressure from emerging resistance. Thus, there is an urgent need for new antimicrobials. The in vitro activity of the newly developed fluoroketolide solithromycin (CEM-101) was evaluated against a collection of 40 M. genitalium strains, including 15 with high-level macrolide resistance and 5 multidrug-resistant strains with resistance to both macrolides and quinolones. Furthermore, the MIC of solithromycin was correlated with mutations in the 23S rRNA gene and in the genes encoding ribosomal proteins L4 and L22. The in vitro results showed that solithromycin has activity against M. genitalium superior to that of other macrolides, doxycycline, and fluoroquinolones. Accordingly, this new fluoroketolide might be an effective option for treatment of M. genitalium infections. However, the efficacy of solithromycin in clinical trials with follow-up for test of cure and detection of genotypic and phenotypic resistance needs to be evaluated prior to widespread use. In a phase 2 clinical trial, solithromycin was highly effective as a single oral dose against C. trachomatis and Neisseria gonorrhoeae, suggesting that solithromycin could be a treatment option for several sexually transmitted infections, including in syndromic treatment of urethral and vaginal discharge.
An Efficient Cache Strategy in Information Centric Networking Vehicle-to-Vehicle Scenario

Information centric networking (ICN) has been recently proposed as a prominent solution for content delivery in vehicular ad hoc networks. By caching the data packets in vehicular unused storage space, vehicles can obtain the replicate of contents from other vehicles instead of original content provider, which reduces the access pressure of content provider and increases the response speed of content request. In this paper, we propose a community similarity and population-based cache policy in an ICN vehicle-to-vehicle scenario. First, a dynamic probability caching scheme is designed by evaluating the community similarity and privacy rating of vehicles. Then, a caching vehicle selection method with hop numbers based on content popularity is proposed to reduce the cache redundancy. Moreover, to lower the cache replacement overhead, we put forward a popularity prediction-based cooperative cache replacement mechanism, which predicts and ranks popular content during a period of time. Simulation results show that the performance of our proposed mechanisms is greatly outstanding in reducing the average time delay and increasing the cache hit ratio and the cache hit distance.
Primers Designed for Amplification of Echinococcus multilocularis DNA Amplify the DNA of Encephalitozoon‐Like Spores in the Polymerase Chain Reaction

ABSTRACT. Microsporidian spores were developed from cells which were grown in vitro from a human liver lesion which was due to larval Echinococcus multilocularis. The microsporidian spores developed in the same fashion as an Encephalitozoon cuniculi. The Encephalitozoon‐like spores were completely separated on Percoll gradients. The separated spores contained DNA capable of amplification by two different primer sets designed for the polymerase chain reaction (PCR) of E. multilocularis DNA. However, the cell DNA from which microsporidium developed was thoroughly insensitive to the PCR using the E. multilocularis primer sets. The results strongly suggested that Encephalitozoon should be taken into consideration, when DNA isolated from larval E. multilocularis is analyzed.
The occurrence of fungi in hospital and community potable waters

The prevalence of fungi was investigated in 126 potable water samples (84 hospital and 42 community samples), in parallel with the standard pollution indicator micro‐organisms. Filamentous fungi were isolated from 104 of 126 (82·5%) samples and yeasts from 14 (11·1%), whereas their mean counts were 36·6 and 4·4, respectively. Fungi were isolated from 95·2% of community and 76·2% of hospital water samples, with the difference being statistically significant (P < 0·05), while yeasts were isolated from 9·5 and 11·9%, respectively. Prevailing genera were Penicillium spp. , isolated from 64, Aspergillus spp. , from 53, and Candida, from nine of the examined samples. Colony‐forming units of yeasts were significantly correlated with those of total and faecal coliforms, whereas the counts of filamentous fungi were significantly correlated with total heterotrophic bacteria counts. These results suggest that tap water is a potential transmission route for fungi both in hospitals and the community in the examined region and may pose a health hazard mainly for the immunocompromised host.