Autohydrolysis Pretreatment of Mixed Softwood to Produce Value Prior to Combustion

Autohydrolysis is a hot water pretreatment to extract soluble components from wood that can be used prior to converting the woody residuals into paper, wood products, fuel, or other goods. In this study, mixed softwood chips were autohydrolyzed in hot water at 150, 160, 170, and 180 °C for 1 and 2 h residence times. The objective was to understand the tradeoff between the extraction of fermentable sugar and the residual solid total energy of combustion quantitatively. This process strategy will be referred to as “value prior to combustion”. High-performance liquid chromatography was used to determine chemical compositions (sugars and byproducts such as acetic acid, furfural, and hydroxymethylfurfural) of the extracted liquid and residuals; a bomb calorimeter was used to measure the heating value of original wood and solid residue. As the autohydrolysis temperature increased, material balances of the system indicated higher volatile byproducts loss. More hemicelluloses were solubilized by the hot water extraction process at higher temperatures and longer residence times, and a greater degree of sugar degradation was also observed. The maximum sugar yield was determined to occur at conditions of 170 °C for 2 h, during which 13 g of sugar was recovered from the extract out of 100 g of oven-dried wood. The heating value of the solid residues after extraction was greater than the original wood. The total energy content of the solid residual after extraction ranged from 85 to 98 % of the original energy content of the feed with higher temperatures reducing the total energy content.     

A Genetic RNAi Screen for IP3/Ca2+ Coupled GPCRs in Drosophila Identifies the PdfR as a Regulator of Insect Flight

Insect flight is regulated by various sensory inputs and neuromodulatory circuits which function in synchrony to control and fine-tune the final behavioral outcome. The cellular and molecular bases of flight neuromodulatory circuits are not well defined. In Drosophila melanogaster, it is known that neuronal IP₃ receptor mediated Ca²⁺ signaling and store-operated Ca²⁺ entry (SOCE) are required for air-puff stimulated adult flight. However, G-protein coupled receptors (GPCRs) that activate intracellular Ca²⁺ signaling in the context of flight are unknown in Drosophila. We performed a genetic RNAi screen to identify GPCRs that regulate flight by activating the IP₃ receptor. Among the 108 GPCRs screened, we discovered 5 IP₃/Ca²⁺ linked GPCRs that are necessary for maintenance of air-puff stimulated flight. Analysis of their temporal requirement established that while some GPCRs are required only during flight circuit development, others are required both in pupal development as well as during adult flight. Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight. From the analysis of PdfR expressing neurons relevant for flight and its well-defined roles in other behavioral paradigms, we propose that PdfR signaling functions systemically to integrate multiple sensory inputs and modulate downstream motor behavior.     

Association of multiple drug resistance-1 gene polymorphism with multiple drug resistance in breast cancer patients from an ethnic Saudi Arabian population

Chemotherapy has been used widely to treat cancer, both as a systemic therapy and as a local treatment. Unfortunately, many types of cancer are still refractory to chemotherapy. The mechanisms of anticancer drug resistance have been extensively explored but have not been fully characterized. This study analyzed the occurrences of polymorphism (SNP) in the MDR1 gene in breast cancer patients and determined a possible association with chemotherapy. The study group included one hundred breast carcinoma patients who subsequently received chemotherapy (the regimen generally consisted of commonly used drugs such as cyclophosphamide, adriamycin, 5-fluorouracil, docetaxel and their combinations). Blood samples from 100 healthy individuals are used, as controls were also genotyped for the MDR1 gene. This investigation revealed a significant correlation with response to various regimens of chemotherapy showing a low response to therapy with the CT/TT genotype at (exon 12) 1236 codon (p < 0.001). These findings demonstrate, for the first time, that the polymorphisms in (exon 12) 1236 codon of the MDR1 gene greatly influence the drug response in patients from the Arab population of Saudi Arabia.     

CD8+ T Cell Cross-Reactivity Profiles and HIV-1 Immune Escape towards an HLA-B35-Restricted Immunodominant Nef Epitope

Antigen cross-reactivity is an inbuilt feature of the T cell compartment. However, little is known about the flexibility of T cell recognition in the context of genetically variable pathogens such as HIV-1. In this study, we used a combinatorial library containing 24 billion octamer peptides to characterize the cross-reactivity profiles of CD8⁺ T cells specific for the immunodominant HIV-1 subtype B Nef epitope VY8 (VPLRPMTY) presented by HLA-B^*35∶01. In conjunction, we examined naturally occurring antigenic variations within the VY8 epitope. Sequence analysis of plasma viral RNA isolated from 336 HIV-1-infected individuals revealed variability at position (P) 3 and P8 of VY8; Phe at P8, but not Val at P3, was identified as an HLA-B^*35∶01-associated polymorphism. VY8-specific T cells generated from several different HIV-1-infected patients showed unique and clonotype-dependent cross-reactivity footprints. Nonetheless, all T cells recognized both the index Leu and mutant Val at P3 equally well. In contrast, competitive titration assays revealed that the Tyr to Phe substitution at P8 reduced T cell recognition by 50–130 fold despite intact peptide binding to HLA-B^*35∶01. These findings explain the preferential selection of Phe at the C-terminus of VY8 in HLA-B^*35∶01⁺ individuals and demonstrate that HIV-1 can exploit the limitations of T cell recognition in vivo.     

A Systematic Review of Risk Factors Associated with Surgical Site Infections among Surgical Patients

Importance

Surgical site infection (SSI) complicates 2-5% of surgeries in the United States. Severity of SSI ranges from superficial skin infection to life-threatening conditions such as severe sepsis, and SSIs are responsible for increased morbidity, mortality, and economic burden associated with surgery. Staphylococcus aureus (S. aureus) is a commonly-isolated organism for SSI, and methicillin-resistant S. aureus SSI incidence is increasing globally.

Objective

The objective of this systematic review was to characterize risk factors for SSI within observational studies describing incidence of SSI in a real-world setting.

Evidence Review

An initial search identified 328 titles published in 2002-2012; 57 were identified as relevant for data extraction. Extracted information included study design and methodology, reported cumulative incidence and post-surgical time until onset of SSI, and odds ratios and associated variability for all factors considered in univariate and/or multivariable analyses.

Findings

Median SSI incidence was 3.7%, ranging from 0.1% to 50.4%. Incidence of overall SSI and S. aureus SSI were both highest in tumor-related and transplant surgeries. Median time until SSI onset was 17.0 days, with longer time-to-onset for orthopedic and transplant surgeries. Risk factors consistently identified as associated with SSI included co-morbidities, advanced age, risk indices, patient frailty, and surgery complexity. Thirteen studies considered diabetes as a risk factor in multivariable analysis; 85% found a significant association with SSI, with odds ratios ranging from 1.5-24.3. Longer surgeries were associated with increased SSI risk, with a median odds ratio of 2.3 across 11 studies reporting significant results.

Conclusions and Relevance

In a broad review of published literature, risk factors for SSI were characterized as describing reduced fitness, patient frailty, surgery duration, and complexity. Recognition of risk factors frequently associated with SSI allows for identification of such patients with the greatest need for optimal preventive measures to be identified and pre-treatment prior to surgery.     

Exosomal and Non-Exosomal Transport of Extra-Cellular microRNAs in Follicular Fluid: Implications for Bovine Oocyte Developmental Competence

Cell-cell communication within the follicle involves many signaling molecules, and this process may be mediated by secretion and uptake of exosomes that contain several bioactive molecules including extra-cellular miRNAs. Follicular fluid and cells from individual follicles of cattle were grouped based on Brilliant Cresyl Blue (BCB) staining of the corresponding oocytes. Both Exoquick precipitation and differential ultracentrifugation were used to separate the exosome and non-exosomal fraction of follicular fluid. Following miRNA isolation from both fractions, the human miRCURY LNA™ Universal RT miRNA PCR array system was used to profile miRNA expression. This analysis found that miRNAs were present in both exosomal and non-exosomal fraction of bovine follicular fluid. We found 25 miRNAs differentially expressed (16 up and 9 down) in exosomes and 30 miRNAs differentially expressed (21 up and 9 down) in non-exosomal fraction of follicular fluid in comparison of BCB- versus BCB+ oocyte groups. Expression of selected miRNAs was detected in theca, granulosa and cumulus oocyte complex. To further explore the potential roles of these follicular fluid derived extra-cellular miRNAs, the potential target genes were predicted, and functional annotation and pathway analysis revealed most of these pathways are known regulators of follicular development and oocyte growth. In order to validate exosome mediated cell-cell communication within follicular microenvironment, we demonstrated uptake of exosomes and resulting increase of endogenous miRNA level and subsequent alteration of mRNA levels in follicular cells in vitro. This study demonstrates for the first time, the presence of exosome or non-exosome mediated transfer of miRNA in the bovine follicular fluid, and oocyte growth dependent variation in extra-cellular miRNA signatures in the follicular environment.     

Effect of Cu,Fe, Mn,Ni, and Zn and Bioaccessibilities in the Hazelnuts Growing in Sakarya,Turkey using In-Vitro Gastrointestinal Extraction Method

Biological Trace Element Research - Total concentrations of heavy metals such as Cu, Fe, Mn, Ni, and Zn in different hazelnut samples obtained by different regions of Sakarya city, Turkey were...     

Virtual high-throughput screening of natural compounds in-search of potential inhibitors for protection of telomeres 1 (POT1)

Communicated by Ramaswamy H. Sarma     

Functional characterization of human myosin-binding protein C3 variants associated with hypertrophic cardiomyopathy reveals exon-specific cardiac phenotypes in zebrafish model

Myosin-binding protein C 3 (MYBPC3) variants are the most common cause of hypertrophic cardiomyopathy (HCM). HCM is a complex cardiac disorder due to its significant genetic and clinical heterogeneity. MYBPC3 variants genotype–phenotype associations remain poorly understood. We investigated the impact of two novel human MYBPC3 splice-site variants: V1: c.654+2_654+4dupTGG targeting exon 5 using morpholino MOe5i5; and V2: c.772+1G>A targeting exon 6 using MOe6i6; located within C1 domain of cMyBP-C protein, known to be critical in regulating sarcomere structure and contractility. Zebrafish MOe5i5 and MOe6i6 morphants recapitulated typical characteristics of human HCM with cardiac phenotypes of varying severity, including reduced cardiomyocyte count, thickened ventricular myocardial wall, a drastic reduction in heart rate, stroke volume, and cardiac output. Analysis of all cardiac morphological and functional parameters demonstrated that V2 cardiac phenotype was more severe than V1. Coinjection with synthetic human MYBPC3 messenger RNA (mRNA) partially rescued disparate cardiac phenotypes in each zebrafish morphant. While human MYBPC3 mRNA partially restored the decreased heart rate in V1 morphants and displayed increased percentages of ejection fraction, fractional shortening, and area change, it failed to revert the V1 ventricular myocardial thickness. These results suggest a possible V1 impact on cardiac contractility. In contrast, attempts to rescue V2 morphants only restored the ventricular myocardial wall hypertrophy phenotype but had no significant effect on impaired heart rate, suggesting a potential V2 impact on the cardiac structure. Our study provides evidence of an association between MYBPC3 exon-specific cardiac phenotypes in the zebrafish model providing important insights into how these genetic variants contribute to HCM disease.