Miracle-dz/UniFAR-FTUs huggingface dataset:
Erg4A and Erg4B Are Required for Conidiation and Azole Resistance via Regulation of Ergosterol Biosynthesis in Aspergillus fumigatus

ABSTRACT Ergosterol, a fungus-specific sterol enriched in cell plasma membranes, is an effective antifungal drug target. However, current knowledge of the ergosterol biosynthesis process in the saprophytic human fungal pathogen Aspergillus fumigatus remains limited. In this study, we found that two endoplasmic reticulum-localized sterol C-24 reductases encoded by both erg4A and erg4B homologs are required to catalyze the reaction during the final step of ergosterol biosynthesis. Loss of one homolog of Erg4 induces the overexpression of the other one, accompanied by almost normal ergosterol synthesis and wild-type colony growth. However, double deletions of erg4A and erg4B completely block the last step of ergosterol synthesis, resulting in the accumulation of ergosta-5,7,22,24(28)-tetraenol, a precursor compound of ergosterol. Further studies indicate that erg4A and erg4B are required for conidiation but not for hyphal growth. Importantly, the Δerg4A Δerg4B mutant still demonstrates wild-type virulence in a compromised mouse model but displays remarkable increased susceptibility to antifungal azoles. Our data suggest that inhibitors of Erg4A and Erg4B may serve as effective candidates for adjunct antifungal agents with azoles. IMPORTANCE Knowledge of the ergosterol biosynthesis pathway in the human opportunistic pathogen A. fumigatus is useful for designing and finding new antifungal drugs. In this study, we demonstrated that the endoplasmic reticulum-localized sterol C-24 reductases Erg4A and Erg4B are required for conidiation via regulation of ergosterol biosynthesis. Moreover, inactivation of both Erg4A and Erg4B results in hypersensitivity to the clinical guideline-recommended antifungal drugs itraconazole and voriconazole. Therefore, our finding indicates that inhibition of Erg4A and Erg4B might be an effective approach for alleviating A. fumigatus infection.
Distribution and Environmental Persistence of the Causative Agent of White-Nose Syndrome, Geomyces destructans, in Bat Hibernacula of the Eastern United States

ABSTRACT White-nose syndrome (WNS) is an emerging disease of hibernating bats caused by the recently described fungus Geomyces destructans. First isolated in 2008, the origins of this fungus in North America and its ability to persist in the environment remain undefined. To investigate the correlation between manifestation of WNS and distribution of G. destructans in the United States, we analyzed sediment samples collected from 55 bat hibernacula (caves and mines) both within and outside the known range of WNS using a newly developed real-time PCR assay. Geomyces destructans was detected in 17 of 21 sites within the known range of WNS at the time when the samples were collected; the fungus was not found in 28 sites beyond the known range of the disease at the time when environmental samples were collected. These data indicate that the distribution of G. destructans is correlated with disease in hibernating bats and support the hypothesis that the fungus is likely an exotic species in North America. Additionally, we examined whether G. destructans persists in infested bat hibernacula when bats are absent. Sediment samples were collected from 14 WNS-positive hibernacula, and the samples were screened for viable fungus by using a culture technique. Viable G. destructans was cultivated from 7 of the 14 sites sampled during late summer, when bats were no longer in hibernation, suggesting that the fungus can persist in the environment in the absence of bat hosts for long periods of time.
Molecular Definition of Vaginal Microbiota in East African Commercial Sex Workers

ABSTRACT Resistance to HIV infection in a cohort of commercial sex workers living in Nairobi, Kenya, is linked to mucosal and antiinflammatory factors that may be influenced by the vaginal microbiota. Since bacterial vaginosis (BV), a polymicrobial dysbiosis characterized by low levels of protective Lactobacillus organisms, is an established risk factor for HIV infection, we investigated whether vaginal microbiology was associated with HIV-exposed seronegative (HESN) or HIV-seropositive (HIV+) status in this cohort. A subset of 44 individuals was selected for deep-sequencing analysis based on the chaperonin 60 (cpn60) universal target (UT), including HESN individuals (n = 16), other HIV-seronegative controls (HIV-N, n = 16), and HIV+ individuals (n = 12). Our findings indicate exceptionally high phylogenetic resolution of the cpn60 UT using reads as short as 200 bp, with 54 species in 29 genera detected in this group. Contrary to our initial hypothesis, few differences between HESN and HIV-N women were observed. Several HIV+ women had distinct profiles dominated by Escherichia coli. The deep-sequencing phylogenetic profile of the vaginal microbiota corresponds closely to BV+ and BV− diagnoses by microscopy, elucidating BV at the molecular level. A cluster of samples with intermediate abundance of Lactobacillus and dominant Gardnerella was identified, defining a distinct BV phenotype that may represent a transitional stage between BV+ and BV−. Several alpha- and betaproteobacteria, including the recently described species Variovorax paradoxus, were found to correlate positively with increased Lactobacillus levels that define the BV− (“normal”) phenotype. We conclude that cpn60 UT is ideally suited to next-generation sequencing technologies for further investigation of microbial community dynamics and mucosal immunity underlying HIV resistance in this cohort.
The Role of Host Phylogeny Varies in Shaping Microbial Diversity in the Hindguts of Lower Termites

ABSTRACT The hindguts of lower termites and Cryptocercus cockroaches are home to a distinct community of archaea, bacteria, and protists (primarily parabasalids and some oxymonads). Within a host species, the composition of these hindgut communities appears relatively stable, but the evolutionary and ecological factors structuring community composition and stability are poorly understood, as are differential impacts of these factors on protists, bacteria, and archaea. We analyzed the microbial composition of parabasalids and bacteria in the hindguts of Cryptocercus punctulatus and 23 species spanning 4 families of lower termites by pyrosequencing variable regions of the small-subunit rRNA gene. Especially for the parabasalids, these data revealed undiscovered taxa and provided a phylogenetic basis for a more accurate understanding of diversity, diversification, and community composition. The composition of the parabasalid communities was found to be strongly structured by the phylogeny of their hosts, indicating the importance of historical effects, although exceptions were also identified. Particularly, spirotrichonymphids and trichonymphids likely were transferred between host lineages. In contrast, host phylogeny was not sufficient to explain the majority of bacterial community composition, but the compositions of the Bacteroidetes, Elusimicrobia, Tenericutes, Spirochaetes, and Synergistes were structured by host phylogeny perhaps due to their symbiotic associations with protists. All together, historical effects probably resulting from vertical inheritance have had a prominent role in structuring the hindgut communities, especially of the parabasalids, but dispersal and environmental acquisition have played a larger role in community composition than previously expected.
The social positioning of older people living with Alzheimer’s disease who scream in long-term care homes

This article describes the social positioning of older people living with Alzheimer’s disease who scream in a long-term care home. Few studies have focused on the social positions taken by older people, their family and formal caregivers during interaction and their effects on screams. A secondary data analysis was conducted using Harré and Van Langenhove’s positioning theory. The results show that older people are capable of positioning and repositioning themselves in relational patterns. Family and formal caregivers position older people who scream according to their beliefs about their lived experience. They also react emotionally to older people and try to influence their behaviors. Understanding the social positioning of older people with Alzheimer’s disease brought out their capacities and their caregivers’ concerns for their well-being. Interventions should focus on these strengths and on promoting healthy relations in the triads to enhance quality of care in long-term care homes.
The Relationship to Death as a Source of Stress for Nurses on a Coronary Care Unit

This paper attempts to understand one of the ways in which nurses on a coronary care unit may be subjected to stress around the problem of establishing a meaningful relationship to death. The themes that nurses expressed during the course of a support group which they had requested are analyzed and discussed. The paper focuses on the stress felt by the nurses over responsibility for controlling illness and death which indicated an unconscious confusion between the feeling of being responsible for the care of an ill or dying patient and the feeling of being responsible for the occurrence of the patient's illness or death. The possible source of this stressful confusion in medicine's and society's own relationship to death is discussed.
Diversity of Dissimilatory Sulfite Reductase Genes (dsrAB) in a Salt Marsh Impacted by Long-Term Acid Mine Drainage

ABSTRACT Sulfate-reducing bacteria (SRB) play a major role in the coupled biogeochemical cycling of sulfur and chalcophilic metal(loid)s. By implication, they can exert a strong influence on the speciation and mobility of multiple metal(loid) contaminants. In this study, we combined DsrAB gene sequencing and sulfur isotopic profiling to identify the phylogeny and distribution of SRB and to assess their metabolic activity in salt marsh sediments exposed to acid mine drainage (AMD) for over 100 years. Recovered dsrAB sequences from three sites sampled along an AMD flow path indicated the dominance of a single Desulfovibrio species. Other major sequence clades were related most closely to Desulfosarcina, Desulfococcus, Desulfobulbus, and Desulfosporosinus species. The presence of metal sulfides with low δ34S values relative to δ34S values of pore water sulfate showed that sediment SRB populations were actively reducing sulfate under ambient conditions (pH of ∼2), although possibly within less acidic microenvironments. Interestingly, δ34S values for pore water sulfate were lower than those for sulfate delivered during tidal inundation of marsh sediments. 16S rRNA gene sequence data from sediments and sulfur isotope data confirmed that sulfur-oxidizing bacteria drove the reoxidation of biogenic sulfide coupled to oxygen or nitrate reduction over a timescale of hours. Collectively, these findings imply a highly dynamic microbially mediated cycling of sulfate and sulfide, and thus the speciation and mobility of chalcophilic contaminant metal(loid)s, in AMD-impacted marsh sediments.
Lactobacillus buchneri Genotyping on the Basis of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Locus Diversity

ABSTRACT Clustered regularly interspaced short palindromic repeats (CRISPR) in combination with associated sequences (cas) constitute the CRISPR-Cas immune system, which uptakes DNA from invasive genetic elements as novel “spacers” that provide a genetic record of immunization events. We investigated the potential of CRISPR-based genotyping of Lactobacillus buchneri, a species relevant for commercial silage, bioethanol, and vegetable fermentations. Upon investigating the occurrence and diversity of CRISPR-Cas systems in Lactobacillus buchneri genomes, we observed a ubiquitous occurrence of CRISPR arrays containing a 36-nucleotide (nt) type II-A CRISPR locus adjacent to four cas genes, including the universal cas1 and cas2 genes and the type II signature gene cas9. Comparative analysis of CRISPR spacer content in 26 L. buchneri pickle fermentation isolates associated with spoilage revealed 10 unique locus genotypes that contained between 9 and 29 variable spacers. We observed a set of conserved spacers at the ancestral end, reflecting a common origin, as well as leader-end polymorphisms, reflecting recent divergence. Some of these spacers showed perfect identity with phage sequences, and many spacers showed homology to Lactobacillus plasmid sequences. Following a comparative analysis of sequences immediately flanking protospacers that matched CRISPR spacers, we identified a novel putative protospacer-adjacent motif (PAM), 5′-AAAA-3′. Overall, these findings suggest that type II-A CRISPR-Cas systems are valuable for genotyping of L. buchneri.
Microbial Gutta-Percha Degradation Shares Common Steps with Rubber Degradation by Nocardia nova SH22a

ABSTRACT Nocardia nova SH22a, a bacterium capable of degrading gutta-percha (GP) and natural rubber (NR), was used to investigate the GP degradation mechanism and the relations between the GP and NR degradation pathways. For this strain, a protocol of electroporation was systematically optimized, and an efficiency of up to 4.3 × 107 CFU per μg of plasmid DNA was achieved. By applying this optimized protocol to N. nova SH22a, a Tn5096-based transposon mutagenesis library of this bacterium was constructed. Among about 12,000 apramycin-resistant transformants, we identified 76 stable mutants defective in GP or NR utilization. Whereas 10 mutants were specifically defective in GP utilization, the growth of the other 66 mutants was affected on both GP and NR. This indicated that the two degradation pathways are quite similar and share many common steps. The larger number of GP-degrading defective mutants could be explained in one of two ways: either (i) the GP pathway is more complex and harbors more specific steps or (ii) the steps for both pathways are almost identical, but in the case of GP degradation there are fewer enzymes involved in each step. The analysis of transposition loci and genetic studies on interesting genes confirmed the crucial role of an α-methylacyl-coenzyme A racemase in the degradation of both GP and NR. We also demonstrated the probable involvement of enzymes participating in oxidoreduction reactions, β-oxidation, and the synthesis of complex cell envelope lipids in the degradation of GP.
Anaerobic Sulfur Metabolism Coupled to Dissimilatory Iron Reduction in the Extremophile Acidithiobacillus ferrooxidans

ABSTRACT Gene transcription (microarrays) and protein levels (proteomics) were compared in cultures of the acidophilic chemolithotroph Acidithiobacillus ferrooxidans grown on elemental sulfur as the electron donor under aerobic and anaerobic conditions, using either molecular oxygen or ferric iron as the electron acceptor, respectively. No evidence supporting the role of either tetrathionate hydrolase or arsenic reductase in mediating the transfer of electrons to ferric iron (as suggested by previous studies) was obtained. In addition, no novel ferric iron reductase was identified. However, data suggested that sulfur was disproportionated under anaerobic conditions, forming hydrogen sulfide via sulfur reductase and sulfate via heterodisulfide reductase and ATP sulfurylase. Supporting physiological evidence for H2S production came from the observation that soluble Cu2+ included in anaerobically incubated cultures was precipitated (seemingly as CuS). Since H2S reduces ferric iron to ferrous in acidic medium, its production under anaerobic conditions indicates that anaerobic iron reduction is mediated, at least in part, by an indirect mechanism. Evidence was obtained for an alternative model implicating the transfer of electrons from S0 to Fe3+ via a respiratory chain that includes a bc 1 complex and a cytochrome c. Central carbon pathways were upregulated under aerobic conditions, correlating with higher growth rates, while many Calvin-Benson-Bassham cycle components were upregulated during anaerobic growth, probably as a result of more limited access to carbon dioxide. These results are important for understanding the role of A. ferrooxidans in environmental biogeochemical metal cycling and in industrial bioleaching operations.
Prevalence of Virulence Genes Associated with Pathogenic Escherichia coli Strains Isolated from Domestically Harvested Rainwater during Low- and High-Rainfall Periods

ABSTRACT The possible health risks associated with the consumption of harvested rainwater remains one of the major obstacles hampering its large-scale implementation in water limited countries such as South Africa. Rainwater tank samples collected on eight occasions during the low- and high-rainfall periods (March to August 2012) in Kleinmond, South Africa, were monitored for the presence of virulence genes associated with Escherichia coli. The identity of presumptive E. coli isolates in rainwater samples collected from 10 domestic rainwater harvesting (DRWH) tanks throughout the sampling period was confirmed through universal 16S rRNA PCR with subsequent sequencing and phylogenetic analysis. Species-specific primers were also used to routinely screen for the virulent genes, aggR, stx, eae, and ipaH found in enteroaggregative E. coli (EAEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), and enteroinvasive E. coli, respectively, in the rainwater samples. Of the 92 E. coli strains isolated from the rainwater using culture based techniques, 6% were presumptively positively identified as E. coli O157:H7 using 16S rRNA. Furthermore, virulent pathogenic E. coli genes were detected in 3% (EPEC and EHEC) and 16% (EAEC) of the 80 rainwater samples collected during the sampling period from the 10 DRWH tanks. This study thus contributes valuable information to the limited data available regarding the ongoing prevalence of virulent pathotypes of E. coli in harvested rainwater during a longitudinal study in a high-population-density, periurban setting.
Contribution of direct obstetric complications to maternal deaths in Makurdi, North-Central Nigeria

Context : The Federal Medical Centre Makurdi is the only tertiary health institution in Benue State. Maternal deaths are a frequent occurrence in the centre thereby necessitating this study. Objective : To determine the maternal mortality ratio, the case fatality rate and the contribution of direct obstetric complications to these deaths. Subjects and Methods : A four month descriptive study of obstetric service data from 1 January to 30 April 2004. Results : During the study period, there were a total of 363 deliveries (52% unbooked, 48% booked, 20% DOC.) and 16 maternal deaths (94% were direct) giving a maternal mortality ratio of 4 408 / 100 000 deliveries.14 (87.5%) of the deaths were unbooked obstetric emergencies. The overall case fatality rate (CFR) was 21%. The contribution of each direct obstetric complication to the direct maternal deaths was as follows: obstructed labour/ ruptured uterus (53.3 %), postpartum haemorrhage (13.35%), puerperal sepsis (13.35 %), Eclampsia (6. 68 %), induced Abortion (6.68 %). The cause- specific CFR was in this order. Ruptured uterus 100%, Puerperal sepsis 100%, Abortion 25%, severe Preeclampsia/Eclampsia 20%, Obstetric haemorrhage 12.5%, obstructed labour 11.4%. The caesarean section rate was 15 %. Facilities to provide life saving functions were lacking and staff commitment was low. Conclusion : Urgent emergency obstetric care training of residents and provision of parenteral antibiotics, anticonvulsants, oxytocics and safe blood for transfusion is recommended. Keywords : maternal mortality, direct obstetric complications, Nigeria Tropical Journal of Obstetrics and Gynaecology Vol. 22(1) 2005: 22: 37-38
The tragedy of errors

In a documentary forming part of its series Gesundheitsmagazin Praxis (Health Magazine Medical Practice) German ZDF TV traced the history of bovine spongiform encephalopathy from 1985, when the first three cases were detected in Kent, to the present, when BSE has definitely become an affliction of the grey matter of European Union politicians. To establish its thesis that the BSE story was a tragedy of errors from its very beginning and that its outcome is all but certain, the programme interviewed several British, Swiss, and German scientists engaged in studies of spongiform encephalopathies. It also included shots of patients with Creutzfeldt-Jakob disease (CJD)—pictures familiar to British television viewers, …
Gongronema latifolium Modulates Rauwolfia vomitoria-Induced Behaviour and Histomorphology of the Cerebral Cortex

Rauwolfia vomitoria (RV) tiene un efecto sedante potente, el que puede provocar graves consecuencias si no es controlado. Se estudio el efecto de Gongronema latifolium (GL) sobre el comportamiento inducido por RV, como tambien en las actividades bioquimicas, e histomorfologia de la corteza cerebral. Dieciocho ratas macho Wistar con un peso promedio de 266 g, fueron separadas en tres Grupos (1­3). El Grupo 1 (control) recibio 0,5 mL de Tween® 20, mientras que a los Grupos 2 y 3 se les administro, durante siete dias, 150 mg/kg de RV y una combinacion de 150 mg/kg de RV y 200 mg/kg de GL (RV + GL), respectivamente. Doce horas despues de los tratamientos y pruebas neuroconductuales de campo abierto, los animales fueron sacrificados. Se analizaron los sueros y cortezas cerebrales, los cuales fueron procesados y tenidos on HE. Se observo menor actividad ambulatoria y de congelacion (p<0,05) en el grupo RV, mientras que no hubo diferencia en la actividad aspartato aminotransferasa serica y de fosfatasa alcalina, asi como tampoco en los niveles de colesterol y trigliceridos sericos en todos los grupos. La neurohistologia cortical cerebral de los grupos RV y RV + GL mostro que la mayoria de las neuronas aparecen hipertrofiadas con nucleos picnoticos, y una menor cantidad celular en comparacion con el grupo control. La RV produce un comportamiento sedante, y cambios neurohistologicos a nivel de la corteza cerebral lo que podria ser modulado al combinarse con GL.
Broadcast channels with confidential messages

Given two discrete memoryless channels (DMC's) with a common input, it is desired to transmit private messages to receiver 1 rate R_{1} and common messages to both receivers at rate R_{o} , while keeping receiver 2 as ignorant of the private messages as possible. Measuring ignorance by equivocation, a single-letter characterization is given of the achievable triples (R_{1},R_{e},R_{o}) where R_{e} is the equivocation rate. Based on this channel coding result, the related source-channel matching problem is also settled. These results generalize those of Wyner on the wiretap channel and of Korner-Marton on the broadcast Channel.