Zinc oxide-decorated polypyrrole/chitosan bionanocomposites with enhanced photocatalytic,antibacterial and anticancer performance

A bio-nanocomposite matrix of polypyrrole grafted ZnO/chitosan (Ppy/C/Z) was synthesized via the in situ polymerization of pyrrole with different weight fractions of ZnO. Incorporation of ZnO nanoparticles with polypyrrole enhances the photocatalytic, antibacterial as well as cytotoxic properties of the resultant composite. Characterizations of the synthesized product were performed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and thermal analysis (TGA and DTA). Surface morphology and particle size were determined by SEM and TEM. The elemental composition of the material was studied by EDX coupled with SEM. Electrochemical surface area was calculated from electrochemical double layer capacitance (EDLC) measurements using cyclic voltammetry. The photocatalytic activity of the composite material was tested by monitoring the degradation of reactive orange-16 (RO-16), Coomassie Brilliant Blue R-250 (CBB-R-250) and Methylene Blue (MB) dyes and the composite was found to be an effective catalyst in the presence of a UV light source. Various scavengers were used to detect the reactive species involved in the photocatalytic process. Furthermore, the stability of the photocatalyst was assessed by recycling experiments. Moreover, the Ppy/C/Z bio-nanocomposite shows potential application with anti-bacterial and anti-cancer activity against Gram-positive and Gram-negative bacterial pathogens and human cancer cell lines (HeLa and MCF-7). The experimental data confirm that the bio-nanocomposite of Ppy/C/Z showed excellent anti-bacterial and anti-cancer activity as compared to a pristine polypyrrole and chitosan formulation (Ppy/C). The apoptosis data with varying concentrations of Ppy/C/Z reveal the remarkable activity against these cancer cell lines.

Bio-nanocomposites were synthesized via grafting polypyrrole/ZnO onto chitosan chain for the photodegradation of organic pollutants and biomedical applications.     

Retinoblastoma (RB1) pocket domain mutations and promoter hyper-methylation in head and neck cancer

Background

The RB1 gene plays a pivotal role in cell cycle regulation. In this case–control study we searched for alterations in the RB1 pocket domain and its promoter region in head and neck cancer (HNC) patients in the Pakistani population.

Methods

For germline mutation analyses, 380 blood samples from HNC patients and 350 blood samples from control individuals were included. Polymerase chain reaction (PCR) and single strand conformational polymorphism (SSCP) assays, followed by sequence analyses, were used for the RB1 pocket domain mutation screens. For the RB1 promoter methylation screens, 72 HNC tumor samples along with adjacent uninvolved tissues were tested using a methylation-specific polymerase chain reaction (MSP) assay.

Results

RB1 (pocket domain and spacer region) sequence analysis revealed one frameshift and seven non-synonymous missense mutations. The frequency of missense mutations in exon 14, i.e., g76474C?>?T, g76475G?>?C and g76476A?>?G, resulting in Arg455Ser, was found to be highest (0.10). Missense mutations g76467G?>?C (exon14), g76468T?>?C (exon14), g77041A?>?T and g77043A?>?T (exon 16), when analyzed via Alamut biosoftware version 2.0, were found to be present in highly conserved amino acids with Align GVGD scores C15 (GV: 0.00 - GD: 21.82), C65 (GV: 0.00 - GD: 83.33) and C65 (GV: 0.00 - GD: 98.69), respectively. These missense mutations were found to be deleterious by SIFT score: 0.00 (median 3.64). RB1 promoter methylation analysis revealed that 16 % of its cytosines (3 % in CpG) were methylated in the HNC tumor samples.

Conclusion

Our findings indicate that both genetic and epigenetic RB1 changes may contribute to the pathogenesis of HNC in the Pakistani population.     

The vacuum geometry effect on neutron transmission and spatial resolution of neutron transmission

Frequently, shields used against radiation contain some vacuum channels. We have therefore considered an infinite slab with a fixed thickness (thickness 20 λ with λ the mean free path of the neutron in the slab) and an infinite plane source of neutrons which arrived on the left side of the slab; transmitted neutrons through the slab to its right side are detected by finite detectors having windows equal to 2λ. This slab contains a vacuum channel. This channel has many legs with several horizontal parts. We used the Monte Carlo method for sampling the neutron history in the slab with a spatial biasing technique in order to accelerate the calculation convergence (Levitt, L. B. (1968) Nuclear Science and Engineering 31, 500–504; Jehouani, A., Ghassoun, J. and Aboubker, A. (1994) In Proceedings of 6th International Symposium on Radiation Physics, Rabat, Morocco). We studied the effects of the angle position and the number of horizontal parts of the channel on the neutron transmission. We have studied the effect of the vacuum channel opening (Artigas, R. and Hungerford, H. E. (1969) Nuclear Science and Engineering 36, 295–303) on the neutron transmission; for several values of this opening we have calculated the neutron transmission probability for each detector position. This study allowed us to determine the optimal conditions of vacuum geometries to improve protection against neutrons.In the second part we considered a shield which consists of a slab and a two-legged vacuum channel with two horizontal parts. The spatial distribution of neutrons transmitted through the protection screen was determined. This distribution shows two peaks. The study was made for different distances between the two horizontal parts. We have determined the smallest distance between the two horizontal parts for which the two peaks can be resolved.     

Pharmaceutical disposal facilitates the mobilization of resistance determinants among microbiota of polluted environment

The emergence of resistance on exposure to pharmaceuticals among microorganisms has raised serious concern in the therapeutic approach against infectious diseases. Effluents discharge from hospitals, industries, and urban settlements containing pharmaceuticals and other toxic compounds into the aquatic ecosystem selects bacterial population against them; thereby promotes acquisition and dissemination of resistant traits among the inhabitant microbiota. The present study was aimed to determine the prevalence and multidrug resistance pattern of Extended Spectrum β-lactamase (ESBL) producing and non-producing bacterial isolates from the heavily polluted Delhi stretch of river Yamuna, India. Additionally, the role of abiotic factors in the dissemination of conjugative plasmids harbouring resistance genes was also studied using E. coli J53 as recipient and resistant E. coli isolates as donor strains. Of the 227 non-duplicate bacterial isolates, 60% (136) were identified as ESBL⁺ and 40% (91) as ESBL. ESBL⁺ isolates were found highly resistant to β-lactam and non-β-lactam classes of antibiotics compared with the ESBL⁻ isolates. 68% of ESBL⁺ and 24% of ESBL⁻ isolates showed an MAR index of ≥0.5. Surprisingly, multidrug resistance (MDR), extensively drug resistance (XDR), and pandrug resistance (PDR) phenotype were observed for 78.6%, 16.9%, and 0.7% of ESBL⁺ and 90%, 3%, and none for PDR among ESBL⁻ isolates. Conjugation under different conditions showed a higher mobilization rate at neutral pH (7–7.5) for ESBL⁺ isolates. Conjugation frequency was maximum at 40 °C for the isolate E. coli MRB6 (4.1 × 10⁻⁵) and E. coli MRE32 (4.89 × 10⁻⁴) and at 35 °C for E. coli MRA11 (4.89 × 10⁻⁵). The transconjugants obtained were found tolerating different concentrations of mercuric chloride (0.0002–0.2 mg/L). Increased biofilm formation for ESBL⁺ isolates was observed on supplementing media with HgCl₂ (2 μg/mL) either singly or in combination with CTX (10 μg/mL). The present study demonstrates that anthropogenically influenced aquatic environments act as a reservoir of MDR, XDR, and even PDR strains; thereby posing a potent public health risk.     

Giant cell tumor along with secondary aneurysmal bone cyst of scapula: A rare presentation

Giant cell tumor (GCT) is a distinctive lesion characterized by the proliferation of multinucleate giant cells in a stroma of mononuclear cells; it is generally seen in skeletally mature individuals. GCT of bone is usually found in the long bones around the knee or in the distal radius of young adults and is unusual in the flat bones. We report a case of GCT of the acromion of the scapula, with a secondary aneurysmal bone cyst, in a 30-year-old female. Based on our review of the English language medical literature, it appears that the occurrence of a GCT along with a secondary aneurysmal bone cyst in flat bones (e.g.. the scapula) is very rare.     

Is digital photography an accurate and precise method for measuring range of motion of the shoulder and elbow?

Background

Accurate measurements of shoulder and elbow motion are required for the management of musculoskeletal pathology. The purpose of this investigation was to compare three techniques for measuring motion. The authors hypothesized that digital photography would be equivalent in accuracy and show higher precision compared to the other two techniques.

Unexpected features of the dark proteome

We surveyed the “dark” proteome–that is, regions of proteins never observed by experimental structure determination and inaccessible to homology modeling. For 546,000 Swiss-Prot proteins, we found that 44–54% of the proteome in eukaryotes and viruses was dark, compared with only ∼14% in archaea and bacteria. Surprisingly, most of the dark proteome could not be accounted for by conventional explanations, such as intrinsic disorder or transmembrane regions. Nearly half of the dark proteome comprised dark proteins, in which the entire sequence lacked similarity to any known structure. Dark proteins fulfill a wide variety of functions, but a subset showed distinct and largely unexpected features, such as association with secretion, specific tissues, the endoplasmic reticulum, disulfide bonding, and proteolytic cleavage. Dark proteins also had short sequence length, low evolutionary reuse, and few known interactions with other proteins. These results suggest new research directions in structural and computational biology.The Protein Data Bank (PDB) (1) of experimentally determined macromolecular structures recently surpassed 110,000 entries—a landmark in understanding the molecular machinery of life. Structure determination lags far behind DNA sequencing, but high-throughput computational modeling (2, 3) can leverage the PDB to provide accurate structural predictions for a large fraction of protein sequences. Thus, structural data now scale with sequencing, providing a wealth of detail about molecular functions.Previous studies have surveyed all sequence and structure data to characterize the “protein universe” [i.e., all proteins from all organisms (4–8)]; from such surveys, we know much of the proteome comprises evolutionarily conserved domains matching relatively few 3D folds (4, 5). These surveys have focused on the “known” and on extrapolating progress toward complete knowledge of all folds in the protein universe. Such studies have guided structural genomics initiatives aimed at determining at least one PDB structure for each distinct fold (8–10).Our work focuses on the structurally “unknown” (i.e., the fraction of the proteome with no detectable similarity to any PDB structure). We call this fraction the “dark proteome”; we believe that studying the dark proteome will clarify future research directions, as studies of dark matter have done in physics (11).The analogy to dark matter has inspired surveys of other “unknown” properties of proteins; for example, Levitt (6) examined “orphan” protein sequences that do not match to known sequence profiles, which he termed the “dark matter of the protein universe,” and Taylor et al. (12) investigated the “dark matter of protein fold space” (i.e., theoretically plausible folds that have not been observed in native proteins). The same analogy has been used in studies of so-called “junk DNA” (13), which revealed a “hidden layer” of noncoding RNAs (14). Could surveying the dark proteome also reveal undiscovered biological systems?In fact, discoveries have already resulted from studying regions of unknown structure, namely, intrinsically disordered regions. Long known to confound structure determination (15)—thus forming part of the dark proteome—disorder was largely ignored until recently (16) and yet is now known to play key functional roles, especially in eukaryotes (17). In addition, there is a second type of region that often has unknown structure and is associated with specific biological functions, namely, transmembrane segments (18). Thus, both disorder and transmembrane regions are “known unknowns” (i.e., we know that they are often “dark”). Could the dark proteome contain “unknown unknowns” (i.e., regions with specific functions that confound structure determination and that we are unaware of)?To address this question, we need to map the dark proteome (i.e., determine all protein regions that cannot be modeled onto any PDB structure). Most available modeling datasets—collected in the Protein Model Portal (PMP) (2)—are not well suited because they aim for breadth of coverage, typically providing only a few PDB matches per protein. Mapping the dark proteome requires depth of coverage, such as the survey of Khafizov et al. (8). (Unfortunately, however, Khafizov et al. used only a few model organisms.) We recently announced Aquaria (19), which provides a median of 35 sequence-to-structure alignments for each Swiss-Prot sequence, a depth of structural data not available from other resources.In this work, we used Aquaria to survey the dark proteome in unprecedented depth. We found most of the dark proteome cannot be readily accounted for and shows unexpected features.