Insight into the molecular mechanism, cytotoxic, and anticancer activities of phyto-reduced silver nanoparticles in MCF-7 breast cancer cell lines.

This contribution insight on the cytotoxic and anticancer activities and molecular mechanism of phyto-reduced silver nanoparticles (AgNPs) in MCF-7 breast cancer cell lines. A simple, entirely green synthesis process was optimized for the phyto-reduction of AgNP (~12.7 nm) using aqueous leaf extracts of Indigofera heterantha. The structural and vibrational properties of biosynthesized AgNPs were extensively characterized using UV-Vis spectrophotometer, x-ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform Infrared spectroscopy (FTIR), while their shape and morphology was studied through scanning electron microscopy (SEM). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay indicates concentration dependent inhibition with IC50, 27.93 ± 2.10 µg/mL against MCF-7 cells and 294.38 ± 3.87 µg/mL against L929 cells. The manifested anticancer mechanism in MCF-7 cells was extensively studied using Acridine orange/ethidium bromide (AO/EB), 4',6-diamidino-2-phenylindole (DAPI) and Annexin-V/propedium iodide fluorescence microscopic assays. The level of reactive oxygen species (ROS) was measured using DCFH-DA fluorescent spectroscopy. Overall, the results show that AgNPs exhibit cytotoxic and apoptotic effect on breast cancer MCF-7 cells by damaging membrane integrity and nuclear fragmentation due to oxidative stress generated by elevated level of ROS. RESEARCH HIGHLIGHTS: Biomimetic synthesis of nano dimension size silver nanoparticles (AgNPs). Characterization of AgNPs through UV-Vis, DLS, XRD, FTIR, and SEM. Cytotoxic and anticancer effects of the biosynthesized AgNPs in L929 fibroblast cells and MCF7 breast cancer respectively. Determination of morphological, and nuclear changes triggered by AgNPs in MCF 7 breast cancer cells using fluorescent microscopy and flow cytometry. Apoptosis induction by AgNPs in cancer cells through oxidative stress generated by reactive oxygen species (ROS).

Autozygosity mapping in consanguineous Pakistani families identifies nine non-overlapping novel linkage intervals for autosomal recessive non-syndromic mental retardation (AR-NSMR); shows genetic heterogeneity for AR-NSMR.

Psychological disturbance (PD) or cerebral dysfunction (CD) covers several clinical areas, and has defining features of mental retardation. Recently, we conducted a study to investigate heritable heterogeneity in Pakistani consanguineous couples with recessive autosomal intellectual abnormalities. A cohort of three consanguineous families with multiple birth defects, belonging two to district lower Dir and one to district Lodhra, were selected for molecular analysis. All the affected individuals in the cohort showed autosomal recessive non-syndromic mental disturbances. DNA was extracted and subjected to Single tagged sequence (STS) marker analyses to all known non-syndromic autosomal recessive mental retardation (NS-ARMR) genes, while autozygosity mapping was performed by advanced SNP techniques. Fragment analyses of the NS-ARMR disease genes CRBN, CC2D2A, PRSS12, GRIK2, TUSC3, and CC2D1A using polymorphic STS markers confirmed these to be contender genes for the alteration. Mapping of autozygosity in all the study subjects using genome study revealed nine novel linkage intervals, i.e. four intervals for MR4, two intervals for MR8 and three intervals for MR13. In spite of being a monogenic condition, autosomal recessive mental retardation shows genetic heterogeneity and several genes are involved in different families; hence, there is a chance for involvement of separate gene in each family.

A Reinforcement Learning Routing Protocol for UAV Aided Public Safety Networks.

In Public Safety Networks (PSNs), the conservation of on-scene device energy is critical to ensure long term connectivity to first responders. Due to the limited transmit power, this connectivity can be ensured by enabling continuous cooperation among on-scene devices through multipath routing. In this paper, we present a Reinforcement Learning (RL) and Unmanned Aerial Vehicle- (UAV) aided multipath routing scheme for PSNs. The aim is to increase network lifetime by improving the Energy Efficiency (EE) of the PSN. First, network configurations are generated by using different clustering schemes. The RL is then applied to configure the routing topology that considers both the immediate energy cost and the total distance cost of the transmission path. The performance of these schemes are analyzed in terms of throughput, energy consumption, number of dead nodes, delay, packet delivery ratio, number of cluster head changes, number of control packets, and EE. The results showed an improvement of approximately 42% in EE of the clustering scheme when compared with non-clustering schemes. Furthermore, the impact of UAV trajectory and the number of UAVs are jointly analyzed by considering various trajectory scenarios around the disaster area. The EE can be further improved by 27% using Two UAVs on Opposite Axis of the building and moving in the Opposite directions (TUOAO) when compared to a single UAV scheme. The result showed that although the number of control packets in both the single and two UAV scenarios are comparable, the total number of CH changes are significantly different.

Influence of Consanguinity and Medication on the Development of Parkinson's Disease.

INTRODUCTION: Parkinson's disease is the second most common neurodegenerative disease. The disease is more prevalent in aged individuals compared to young ones. AIM: The present study aimed to investigate the factors associated with PD in the population of Khyber Pakhtunkhwa, Pakistan. METHODS: In this study, the questionnaire was filled from 600 PD patients, which include 54 familial cases, and 1,200 control subjects. To study the risk of PD in familial cases, questionnaires were also filled from the cases and controls. RESULTS: This study revealed that depression symptomology is common in PD patients. Moreover, the risk of PD was higher in patients with consanguineous marriages compare to controls (OR = 3.96, 95% Cl = 1.98-7.89). The first-degree relatives (59.3%) of PD patients are more likely to develop PD compared to a second- (29.5%) or third-degree (11.1%) relatives. Furthermore, the risk of PD is higher in individuals whose parents get married to first-cousin (OR: 4.76, 95% Cl: 1.81-12.5) than second- (OR: 1.34, 95% Cl: 0.54-3.32) or third-cousin marriages (OR = 0.18, 95% Cl: 0.06-0.49). Moreover, the use of paracetamol (OR: 0.39; 95% Cl: 0.25-0.59) and ibuprofen (OR: 0.35; 95% Cl: 0.17-0.70) were higher in control subjects. CONCLUSION: This study concludes that consanguineous marriages and first-degree relation with PD patients increase the risk of PD, while the use of certain medications may decrease the risk of PD. Further study is warranted in a population of Pakistan.

Diversity and Distribution of Cryptic Species of the Bemisia tabaci (Hemiptera: Aleyrodidae) complex in Pakistan.

Bemisia tabaci (Gennadius; Hempitera: Aleyrodidae) is considered to be a cryptic (sibling) species complex, the members of which exhibit morphological invariability while being genetically and behaviorally distinct. Members of the complex are agricultural pests that cause direct damage by feeding on plants, and indirectly by transmitting viruses that cause diseases leading to reduced crop yield and quality. In Pakistan, cotton leaf curl disease, caused by multiple begomovirus species, is the most economically important viral disease of cotton. In the study outlined here, the diversity and geographic distribution of B. tabaci cryptic species was investigated by analyzing a taxonomically informative fragment of the mitochondrial cytochrome c oxidase 1 gene (mtCOI-3'). The mtCOI-3' sequence was determined for 285 adult whiteflies and found to represent six cryptic species, the most numerous being Asia II-1 and Middle East Asia Minor 1 (MEAM-1), the later also referred to as the B-biotype, which was previously thought to be confined to Sindh province but herein, was also found to be present in the Punjab province. The endemic Asia I was restricted to Sindh province, while an individual in the Asia II-8 was identified in Pakistan for the first time. Also for the first time, samples were collected from northwestern Pakistan and Asia II-1 was identified. Results indicate that in Pakistan the overall diversity of B. tabaci cryptic species is high and, based on comparisons with findings from previous studies, the distribution is dynamic.

Further changes in the cotton leaf curl disease complex: an indication of things to come?

Cotton leaf curl disease (CLCuD) has been a problem for cotton production in Pakistan and India since the early 1990s. The disease is caused by begomoviruses associated with a specific satellite, the cotton leaf curl Multan betasatellite (CLCuMB). In 2001, resistance introduced into cotton was broken by a recombinant begomovirus, Cotton leaf curl Kokhran virus strain Burewala (CLCuKoV-Bur). Unusually, in resistant cotton, this virus lacked an intact transcriptional activator protein (TrAP) gene, with the capacity to encode only 35 of the usual ~134 amino acids. Recently, isolates of CLCuKoV-Bur with a longer, but still truncated, TrAP gene have been identified in cotton breeding lines lacking the earlier resistance. This suggests that more pathogenic viruses with a full TrAP could return to cotton if the earlier resistance is not maintained in ongoing breeding efforts to produce CLCuD-resistant cotton varieties. This conclusion is supported by recent studies showing the reappearance of pre-resistance-breaking begomoviruses, with full-length TrAP genes, in cotton.

Health hazards and adoption of personal protective equipment during cotton harvesting in Pakistan.

The use of personal protective equipment (PPE) during cotton harvesting is critical for securing better health for female cotton pickers in the developing countries where health facilities are not sufficiently available to the masses in the rural areas. Despite increasing the efforts in increasing awareness about the benefits of PPE among the farm workers, a vast majority of the farm workers including pickers don't use the PPE. The present study examines health impacts of cotton harvesting in Pakistani Punjab along with the factors affecting the use of PPE among the cotton pickers. Cross-sectional data collected from Vehari district is used. The study estimates health cost and the use of PPE among the young and elder cotton pickers. Headache, sleeplessness, cough, flue/fever, skin and eyes problems are reported by the young and elder cotton pickers. Personal protective equipment is rarely used during picking. However, the young pickers relatively adopt more PPE compared to the elder cotton pickers. Health cost of cotton picking is US$2.96 and 3.06 per season during the year for the young and elder cotton pickers, respectively. Results of logit model show that health cost, age, education below 8th grade, perception of temporary impact and health problems are important determinants of adopting PPE among the cotton pickers. The findings of the study conclude that the use of PPE can be realized through proper training and education of cotton pickers and farm workers.

Infectivity, effects on helper viruses and whitefly transmission of the deltasatellites associated with sweepoviruses (genus Begomovirus, family Geminiviridae).

Begomoviruses (family Geminiviridae) are whitefly-transmitted viruses with single-stranded DNA genomes that are frequently associated with DNA satellites. These satellites include non-coding satellites, for which the name deltasatellites has been proposed. Although the first deltasatellite was identified in the late 1990s, little is known about the effects they have on infections of their helper begomoviruses. Recently a group of deltasatellites were identified associated with sweepoviruses, a group of phylogenetically distinct begomoviruses that infect plants of the family Convolvulaceae including sweet potato. In this work, the deltasatellites associated with sweepoviruses are shown to be transreplicated and maintained in plants by the virus with which they were identified, sweet potato leaf curl virus (SPLCV). These deltasatellites were shown generally to reduce symptom severity of the virus infection by reducing virus DNA levels. Additionally they were shown to be maintained in plants, and reduce the symptoms induced by two Old World monopartite begomoviruses, tomato yellow leaf curl virus and tomato yellow leaf curl Sardinia virus. Finally one of the satellites was shown to be transmitted plant-to-plant in the presence of SPLCV by the whitefly vector of the virus, Bemisia tabaci, being the first time a deltasatellite has been shown to be insect transmitted.

Diversity in Betasatellites Associated with Cotton Leaf Curl Disease During Source-To-Sink Movement Through a Resistant Host.

Cotton leaf curl is devastating disease of cotton characterized by leaf curling, vein darkening and enations. The disease symptoms are induced by DNA satellite known as Cotton leaf curl Multan betasatellite (CLCuMuB), dominant betasatellite in cotton but another betasatellite known as Chili leaf curl betasatellite (ChLCB) is also found associated with the disease. Grafting experiment was performed to determine if host plant resistance is determinant of dominant population of betasatellite in cotton (several distinct strains of CLCuMuB are associated with the disease). Infected scion of Gossypium hirsutum collected from field (the source) was grafted on G. arboreum, a diploid cotton species, resistant to the disease. A healthy scion of G. hirsutum (sink) was grafted at the top of G. arboreum to determine the movement of virus/betasatellite to upper susceptible scion of G. hirsutum. Symptoms of disease appeared in the upper scion and presence of virus/betasatellite in the upper scion was confirmed via molecular techniques, showing that virus/betasatellite was able to move to upper scion through resistant G. arboreum. However, no symptoms appeared on G. arboreum. Betasatelites were cloned and sequenced from lower scion, upper scion and G. arboreum which show that the lower scion contained both CLCuMuB and ChLCB, however only ChLCB was found in G. arboreum. The upper scion contained CLCuMuB with a deletion of 78 nucleotides (nt) in the non-coding region between A-rich sequence and ßC1 gene and insertion of 27 nt in the middle of ßC1 ORF. This study may help in investigating molecular basis of resistance in G. arboreum.

Complete genome sequences of two novel begomoviruses infecting common bean in Venezuela.

The complete genome sequences of isolates of two new bipartite begomoviruses (genus Begomovirus, family Geminiviridae) found infecting common bean in Venezuela are provided. The names proposed for each of these viruses are "bean yellow chlorosis virus" (BYCV) and "bean white chlorosis mosaic virus" (BWCMV). Phylogenetic analysis showed that they segregated in two distinct clades of New World begomoviruses. This is the first report of begomoviruses infecting common bean in Venezuela.