Polyhydroxyalkanoates: Properties and chemical modification approaches for their functionalization

Polyhydroxyalkanoates (PHAs) have become an attractive biomaterial in research in the past few years due to their extensive potential industrial applications. Being long chain hydroxyl fatty acid molecules, the PHAs are hydrophobic in nature, and have less functional groups. These features limit their applications in various areas. To enhance their usage, these polymers may need to be modified including surface and chemical modifications. Such modifications may alter their mechanical properties, surface structure, amphiphilic character and rate of degradation to fulfil the requirements for their future applications. Chemical modifications allow incorporation of functional groups to PHAs that could not be introduced through biotechnological methods. These chemically reformed PHAs, with enhanced properties, could be used for broad range of applications. This review aims to introduce different chemical modification approaches including some recent methods that had not been explored or discussed so far for PHAs as possible technologies for widening the range of product and application potentials. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:29–41, 2018     

PABPN1-Dependent mRNA Processing Induces Muscle Wasting

Poly(A) Binding Protein Nuclear 1 (PABPN1) is a multifunctional regulator of mRNA processing, and its expression levels specifically decline in aging muscles. An expansion mutation in PABPN1 is the genetic cause of oculopharyngeal muscle dystrophy (OPMD), a late onset and rare myopathy. Moreover, reduced PABPN1 expression correlates with symptom manifestation in OPMD. PABPN1 regulates alternative polyadenylation site (PAS) utilization. However, the impact of PAS utilization on cell and tissue function is poorly understood. We hypothesized that altered PABPN1 expression levels is an underlying cause of muscle wasting. To test this, we stably down-regulated PABPN1 in mouse tibialis anterior (TA) muscles by localized injection of adeno-associated viruses expressing shRNA to PABPN1 (shPab). We found that a mild reduction in PABPN1 levels causes muscle pathology including myofiber atrophy, thickening of extracellular matrix and myofiber-type transition. Moreover, reduced PABPN1 levels caused a consistent decline in distal PAS utilization in the 3’-UTR of a subset of OPMD-dysregulated genes. This alternative PAS utilization led to up-regulation of Atrogin-1, a key muscle atrophy regulator, but down regulation of proteasomal genes. Additionally reduced PABPN1 levels caused a reduction in proteasomal activity, and transition in MyHC isotope expression pattern in myofibers. We suggest that PABPN1-mediated alternative PAS utilization plays a central role in aging-associated muscle wasting.     

The first replacement of a chlorosulphonyloxy group by chlorine at C-2 in methyl α-D-glucopyranoside and sucrose derivatives

Treatment of methyl 3-O-acetyl-4,6-O-benzylidene-α-D-glucopyranoside 2-chlorosulphate (2), 3,4,6,3′,4′,6′-hexa-O-acetylsucrose 2,1′-bis(chlorosulphate), 3,4,6,3′,4′,6′-hexa-O-acetyl-1′-O-benzoylsucrose 2-chlorosulphate, and 3,4,3′,4′-tetra-O-acetyl-6,6′-dichloro-6,6′-dideoxysucrose 2,1′-bis(chlorosulphate) with lithium chloride in hexamethylphosphoric triamide gave the corresponding chlorodeoxy-manno derivatives. Treatment of the 2-chlorosulphate 2 with such nucleophilic reagents as lithium bromide, sodium azide, sodium chloride, and sodium benzoate in hexamethylphosphoric triamide gave the 2-hydroxy compound as a major product. Selective chlorination at C-1′ was achieved when 3,4,6,3′,4′,6′-hexa-O-acetylsucrose was treated with sulphuryl chloride in a mixture of pyridine and chloroform.     

Ecdysteroids from the flowers of Aerva javanica

Four new ecdysteroids (1–4), along with three known steroids, β-ecdysone (5), 5-β-2-deoxyintegristerone A (6) and 24-epi-makisterone A (7) (Fig. 1), were isolated from the methanolic extract of the flowers of Aerva javanica by using normal and reverse phase chromatography. The structures of the new compounds (1–4) were determined due to 1D (¹H and ¹³C), 2D NMR (HSQC, HMBC, COSY, NOESY) techniques and high resolution mass spectrometry (HREIMS). The known compounds (5–7) were characterized based on the 1D NMR spectroscopy and mass spectrometry and by comparison with the literature values. All isolates were evaluated for their inhibitory activities against enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX).     

An exploration of how litter controls drainage water DIN, DON and DOC dynamics in freely draining acid grassland soils

Surface and subsurface litter fulfil many functions in the biogeochemical cycling of C and N in terrestrial ecosystems. These were explored using a microcosm study by monitoring dissolved inorganic nitrogen (DIN) (NH₄ ⁺–N?+?NO₃ ^?–N), dissolved organic nitrogen (DON) and dissolved organic carbon (DOC) concentrations and fluxes in drainage water under ambient outdoor temperatures. Subsurface litter remarkably reduced the DIN concentrations in winter, probably by microbial N uptake associated with higher C:N ratio of added litter compared with soil at 10–25?cm depth. Fluxes of DIN were generally dominated by NO₃ ^?–N; but NH₄ ⁺–N strongly dominated DIN fluxes during freeze–thaw events. Appreciable concentrations of NH₄ ⁺–N were observed in the drainage from the acid grassland soils throughout the experiment, indicating NH₄ ⁺–N mobility and export in drainage water especially during freeze–thaw. Litter contributed substantially to DOC and DON production and they were correlated positively (p?<?0.01) for all treatments. DOC and DON concentrations correlated with temperature for the control (p?<?0.01) and surface litter (p?<?0.001) treatments and they were higher in late summer. The subsurface litter treatment, however, moderated the effect of temperature on DOC and DON dynamics. Cumulative N species fluxes confirmed the dominance of litter as the source of DON and DOC in the drainage water. DON constituted 42, 46 and 62% of cumulative TDN flux for control, surface litter and subsurface litter treatments respectively.     

Insecticidal Potential of α-Pinene and β-Caryophyllene against <i>Myzus persicae</i> and Their Impacts on Gene Expression

Myzus persicae (M. persicae) is now considered a threat to agricultural crops due to economic losses. Numerous synthetic insecticides applied every year against M. persicae, are reported to be unsafe for environment, humans, and beneficial insects. Furthermore, several species of Myzus have been found to develop resistance due to over application of these insecticides. Therefore, it is required to find some novel insecticide that would be safe for the environment as well as for humans. In the current study, two major pure constituents α-pinene and β-caryophyllene were evaluated for their insecticidal potential against M. persicae using a fumigant toxicity assay. Furthermore, impact of α-pinene and β-caryophyllene on expression of five different genes, e.g., HSP 60, FPPS I, OSD, TOL and ANT responsible for reproduction, dispersion, and growth of M. persicae has also been investigated. To perform fumigant toxicity assay, five different concentrations (3.5, 4, 4.5, 5 and 6 μL L⁻¹) of α-pinene and β-caryophyllene were prepared. Lethal concentration (LC) was calculated, and gene expression studies were executed through qRT PCR at LC₃₀ of α-pinene and β-caryophyllene. Both constituents demonstrated excellent fumigant toxicity effects against M. persicae at all five concentrations. However, α-pinene shows significantly better results (98%) as compared to β-caryophyllene (80%) after 72 h at 6 μL L⁻¹ of dose. The highest upregulation in expression was demonstrated at LC₃₀ dose of α-pinene in five in three out of five genes understudy (TOL, ANT, and FPPS I). Conversely, two genes HSP 60 and OSD demonstrated downregulation at LC₃₀ dose of β-caryophyllene. Conclusively, our results highlighted the promising insecticidal potential of both compounds α-pinene and β-caryophylleneby interfering with the reproduction and development related processes in M. persicae, allowing us to recommend the phytoconstituents under investigation as an ecofriendly alternative to synthetic insecticides.     

Genetic characterization of <Emphasis Type="Italic">Vitis</Emphasis> germplasm collected from the southwestern US and Mexico to expedite Pierce’s disease-resistance breeding

Pierce’s disease (PD) limits the cultivation of Vitis vinifera grape cultivars in California, across the southern United States and into South America. Resistance has been well characterized in V. arizonica, and one resistance locus has been identified (PdR1). However, resistance is poorly characterized in most other grape species. We tested a wide range of Vitis species from the southwestern United States for resistance to PD and used nuclear and chloroplast markers to phenotypically and genetically select a diverse set of resistant accessions. Chloroplast SSR markers identified 11 maternal lineage lines within the set of 17 (14 new and three previously identified) PD resistant accessions. A total of 19 breeding populations (F1 and pseudo-BC1) were developed with the 14 PD resistant accessions, and a total of 705 seedlings were analyzed for PD resistance. Using a limited mapping approach, 12 SSR markers, linked to the PdR1 locus, were used to genotype the breeding populations and phenotypic data were analyzed. Nine accessions had a major resistance quantitative trait locus (QTL) within the genomic region containing PdR1. The phenotypic data for these three resistant accessions, ANU67, b41-13, and T03-16, did not associate with PdR1 linked markers, indicating that their resistance is located in other regions of the genome. These three accessions were identified as candidates for use in the development of framework maps with larger populations capable of detecting additional and unique loci for PD resistance breeding and the stacking of PD resistance genes.     

Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis

BackgroundNeonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR.Methods and findingsAll studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria.ConclusionsGram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.

Sophie Wen and co-workers report a meta-analysis on bacterial isolates and antimicrobial resistance in neonatal sepsis in low- and lower-middle-income countries.