Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of west-central African origin.

An unusual human retrovirus was isolated from two patients with persistent generalized lymphadenopathy who originate from West-Central Africa and are currently residing in Belgium. Although the virus shared a number of the same biological and morphological properties as human immunodeficiency retrovirus type 1 (HIV-1) and HIV-2, significant antigenic differences could be demonstrated. Several of the viral proteins also differed in molecular weight from the corresponding HIV-1 and HIV-2 proteins. Partial chemical cleavage of the most highly conserved viral proteins resulted in patterns which differed from those of HIV-1 and HIV-2. Furthermore, nucleic acid hybridization experiments were capable of discriminating between the virus types. Sequence analysis of the viral U3 region revealed a unique enhancer organization not found in other immunodeficiency viruses. The data indicated that the new isolate is more closely related to HIV-1 than to HIV-2 but clearly differs in a number of important respects.     

Cloning, nucleotide sequence, and expression of the Brucella melitensis bp26 gene coding for a protein immunogenic in infected sheep

Abstract We have previously identified a Brucella melitensis 28 kDa cytosoluble protein (CP28) which was highly immunogenic in infected sheep and which in addition made possible the serological differentiation between infected and B. melitensis Rev.l vaccinated sheep. Monoclonal antibodies against CP28 were used to screen a B. melitensis 16M genomic library and to clone the corresponding gene. DNA sequencing of the gene encoding CP28 of B. melitensis 16M revealed that it was nearly identical to that of the recently published bp26 gene of Brucella abortus vaccine strain S19 coding for a periplasmic protein. The differences between the B. melitensis 16M gene and that of B. abortus S19 consisted of single nucleotide substitutions, one or two codon deletions, one codon addition, and most importantly a 21-bp deletion. The corresponding region of B. abortus S19 contains two 10-bp direct repeats which could have been involved in the genesis of the deletion. Expression of the B. melitensis 16M bp26 gene in Escherichia coli studied by the use of the monoclonal antibodies showed the same characteristics as reported for the B. abortus S19 bp26 gene, i.e. the presence of a higher molecular mass preprotein and a lower molecular mass band which probably corresponds to the mature protein exported to the periplasm. Immunoblotting performed with sera from either naturally infected or B. melitensis H38 experimentally infected sheep confirmed the importance of the B. melitensis CP28/BP26 protein as diagnostic antigen.     

Aptamer-functionalized quantum dots as theranostic nanotools against cancer and bacterial infections: A comprehensive overview of recent trends

Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics.     

Elevated atmospheric [CO2] can dramatically increase wheat yields in semi‐arid environments and buffer against heat waves

Wheat production will be impacted by increasing concentration of atmospheric CO₂ [CO₂], which is expected to rise from about 400 μmol mol^?1 in 2015 to 550 μmol mol^?1 by 2050. Changes to plant physiology and crop responses from elevated [CO₂] (e[CO₂]) are well documented for some environments, but field‐level responses in dryland Mediterranean environments with terminal drought and heat waves are scarce. The Australian Grains Free Air CO₂ Enrichment facility was established to compare wheat (Triticum aestivum) growth and yield under ambient (~370 μmol^?1 in 2007) and e[CO₂] (550 μmol^?1) in semi‐arid environments. Experiments were undertaken at two dryland sites (Horsham and Walpeup) across three years with two cultivars, two sowing times and two irrigation treatments. Mean yield stimulation due to e[CO₂] was 24% at Horsham and 53% at Walpeup, with some treatment responses greater than 70%, depending on environment. Under supplemental irrigation, e[CO₂] stimulated yields at Horsham by 37% compared to 13% under rainfed conditions, showing that water limited growth and yield response to e[CO₂]. Heat wave effects were ameliorated under e[CO₂] as shown by reductions of 31% and 54% in screenings and 10% and 12% larger kernels (Horsham and Walpeup). Greatest yield stimulations occurred in the e[CO₂] late sowing and heat stressed treatments, when supplied with more water. There were no clear differences in cultivar response due to e[CO₂]. Multiple regression showed that yield response to e[CO₂] depended on temperatures and water availability before and after anthesis. Thus, timing of temperature and water and the crop's ability to translocate carbohydrates to the grain postanthesis were all important in determining the e[CO₂] response. The large responses to e[CO₂] under dryland conditions have not been previously reported and underscore the need for field level research to provide mechanistic understanding for adapting crops to a changing climate.     

Crystal structure of native and a mutant of Lampyris turkestanicus luciferase implicate in bioluminescence color shift

Firefly bioluminescence reaction in the presence of Mg^2 +, ATP and molecular oxygen is carried out by luciferase. The luciferase structure alterations or modifications of assay conditions determine the bioluminescence color of firefly luciferase. Among different beetle luciferases, Phrixothrix hirtus railroad worm emits either yellow or red bioluminescence color. Sequence alignment analysis shows that the red-emitter luciferase from Phrixothrix hirtus has an additional arginine residue at 353 that is absent in other firefly luciferases. It was reported that insertion of Arg in an important flexible loop350–359 showed changes in bioluminescence color from green to red and the optimum temperature activity was also increased. To explain the color tuning mechanism of firefly luciferase, the structure of native and a mutant (E354R/356R/H431Y) of Lampyris turkestanicus luciferase is determined at 2.7 Å and 2.2 Å resolutions, respectively. The comparison of structure of both types of Lampyris turkestanicus luciferases reveals that the conformation of this flexible loop is significantly changed by addition of two Arg in this region. Moreover, its surface accessibility is affected considerably and some ionic bonds are made by addition of two positive charge residues. Furthermore, we noticed that the hydrogen bonding pattern of His431 with the flexible loop is changed by replacing this residue with Tyr at this position. Juxtaposition of a flexible loop (residues 351–359) in firefly luciferase and corresponding ionic and hydrogen bonds are essential for color emission.     

Can Inpatient Hospital Experiences Predict Central Line-Associated Bloodstream Infections?

Background

Factors that increase the risk of central line-associated bloodstream infections (CLABSIs) are not fully understood. Recently, Hospital Compare began compiling data from hospital-required reporting to the CDC''s National Healthcare Safety Network on CLABSIs in intensive care units (ICUs), at over 4,000 Medicare-certified hospitals in the United States, and made this data accessible on a central website. Also available on the same website are results from the Hospital Consumer Assessment of Healthcare Providers and Systems survey of patients'' hospital experiences. Utilizing both databases, our objective was to determine whether patients'' hospital experiences were significantly associated with increased risk for reported ICU CLABSI.

Methods and Findings

We conducted a zero-inflated Poisson regression analysis at the hospital level on CLABSI-observed cases by ICUs in acute care hospitals (n = 1987) in the United States between January 1, 2011, and December 31, 2011. During this period there were a total of 10,866 CLABSI cases and 9,543,765 central line days. In our final model, the percent of patients who reported that they “sometimes” or “never” received help as soon as they wanted was significantly associated with an increased risk for CLABSIs.

Conclusions

Using national datasets, we found that inpatients'' hospital experiences were significantly associated with an increased risk of ICU reported CLABSIs. This study suggests that hospitals with lower staff responsiveness, perhaps because of an understaffing of nurse and supportive personnel, are at an increased risk for CLABSIs. This study bolsters the evidence that patient surveys may be a useful surrogate to predicting the incidence of hospital acquired conditions, including CLABSIs. Moreover, our study found that poor staff responsiveness may be indicative of greater hospital problems and generally poorly performing hospitals; and that this finding may be a symptom of hospitals with a multitude of problems, including patient safety problems, and not a direct cause.     

Assessment of grain quality in terms of functional group response to elevated [CO2], water,and nitrogen using a meta‐analysis: Grain protein,zinc, and iron under future climate

The increasing [CO₂] in the atmosphere increases crop productivity. However, grain quality of cereals and pulses are substantially decreased and consequently compromise human health. Meta‐analysis techniques were employed to investigate the effect of elevated [CO₂] (e[CO₂]) on protein, zinc (Zn), and iron (Fe) concentrations of major food crops (542 experimental observations from 135 studies) including wheat, rice, soybean, field peas, and corn considering different levels of water and nitrogen (N). Each crop, except soybean, had decreased protein, Zn, and Fe concentrations when grown at e[CO₂] concentration (≥550 μmol/mol) compared to ambient [CO₂] (a[CO₂]) concentration (≤380 μmol/mol). Grain protein, Zn, and Fe concentrations were reduced under e[CO₂]; however, the responses of protein, Zn, and Fe concentrations to e[CO₂] were modified by water stress and N. There was an increase in Fe concentration in soybean under medium N and wet conditions but nonsignificant. The reductions in protein concentrations for wheat and rice were ~5%–10%, and the reductions in Zn and Fe concentrations were ~3%–12%. For soybean, there was a small and nonsignificant increase of 0.37% in its protein concentration under medium N and dry water, while Zn and Fe concentrations were reduced by ~2%–5%. The protein concentration of field peas decreased by 1.7%, and the reductions in Zn and Fe concentrations were ~4%–10%. The reductions in protein, Zn, and Fe concentrations of corn were ~5%–10%. Bias in the dataset was assessed using a regression test and rank correlation. The analysis indicated that there are medium levels of bias within published meta‐analysis studies of crops responses to free‐air [CO₂] enrichment (FACE). However, the integration of the influence of reporting bias did not affect the significance or the direction of the [CO₂] effects.     

Response to different sources of vitamin E orally injected and to various doses of vitamin E in calf starter on the plasma vitamin E level in calves around weaning

Calves often face a lower plasma vitamin E level than the recommended level (3 µg/ml for adult cows) after weaning, a level which has been related to a good immune response. Two experiments were performed to determine the most effective source and level of vitamin E to be included in a calf starter to maintain the plasma vitamin E level above the recommended level after weaning. Experiment 1 (Exp 1) and experiment 2 (Exp 2) included a total of 32 and 40 calves, respectively, from 2 weeks before weaning until 2 weeks after weaning. In Exp 1, calves were orally injected a daily dose of different vitamin E sources including, no α-tocopherol (0 dose; Control), 200 mg/d of RRR-α-tocopherol (ALC), 200 mg/d of RRR-α-tocopheryl acetate (ACT), or 200 mg/d of all-rac-α-tocopheryl acetate (SYN). In Exp 2, a dose response study was carried out with 0, 60, 120, and 200 mg/kg of ALC in a pelleted calf starter. Final BW (100 ± 16 and 86 ± 11 kg) and average daily gain (956 ± 303 and 839 ± 176 g/d in Exp 1 and 2, respectively; mean ± SD) were unaffected by either source or level of α-tocopherol. In Exp 1, the plasma RRR-α-tocopherol level was affected by α-tocopherol source (P < 0.001), week (P < 0.001), and interaction between them (P < 0.001). At weaning time, the plasma RRR-α-tocopherol was 2.7, 2.1, 1.1, and 0.8 μg/ml in ALC, ACT, SYN, and Control, respectively. In Exp 2, the plasma α-tocopherol level was affected by ALC dose (P = 0.04), week (P < 0.001), and a tendency for an interaction between them was observed (P = 0.06). At weaning, a 36, 31, and 28% reduction in plasma α-tocopherol level was observed compared to the beginning of the experiment with 0, 60, and 120 mg/kg of ALC, respectively; however, with 200 mg/kg of ALC, a 9% increase in the plasma α-tocopherol level was observed. In addition, 200 mg/kg of ALC was able to maintain plasma α-tocopherol after weaning higher than the recommended level. The results showed that the ALC was the most efficient source of α-tocopherol supplementation to be used in a calf starter. In addition, the 200 mg/kg of ALC in the calf starter was the only effective dose to maintain the postweaning plasma vitamin E concentration at the recommended level after weaning and α-tocopherol similar to that observed before weaning.     

Therapeutic potency of Wnt signaling antagonists in the pathogenesis of prostate cancer,current status and perspectives

Prostate cancer is a major cause of cancer-related death in males. Wnt/β-catenin signaling plays a critical role in the pathogenesis of this disease by regulating angiogenesis, drug resistance, cell proliferation, and apoptosis. Suppression of Wnt canonical or noncanonical signaling pathways via Wnt biological or pharmacological antagonists is a potentially novel therapeutic approach for patients with prostate cancer. This review summarizes the role of Wnt signaling inhibitors in the pathogenesis of prostate cancer for a better understanding and hence a better management of this disease.