Quantitative proteomics analysis of zebrafish exposed to sub-lethal dosages of β-methyl-amino-L-alanine (BMAA)

The non-protein amino acid β-methylamino-L-alanine (BMAA) is a neurotoxin present in microalgae and shown to accumulate in the food web. BMAA has been linked to the complex neurodegenerative disorder of Guam and to increased incidents sporadic ALS. Two main neurotoxic routes are suggested; an excitotoxic by acting as an agonist towards glutamate receptors and a metabolic by misincorporating into cellular proteins. We have used zebrafish, an increasingly used model for neurodegenerative diseases, to further identify signaling components involved in BMAA-induced toxicity. Zebrafish embryos were exposed to sub-lethal dosages of BMAA and a label-free proteomics analysis was conducted on larvae 4 days post fertilization. The exposed larvae showed no developmental abnormalities, but a reduced heart rate and increased expression of GSK3 isoforms. Search towards a reviewed database containing 2968 entries identified 480 proteins. Only 17 of these were regulated 2-fold or more in the exposed larvae. Seven of these proteins could be associated to glutamate receptor signaling and recycling. The remaining nine have all been linked to disturbance in protein homeostasis, reactive oxygen species (ROS) development or neuronal cell death. We also found that BMAA influenced the endocannabinoid system by up-regulation of fatty acid amide hydrolase (FAAH) and that FAAH inhibitor URB597 reduced the BMAA effect on heart rate and GSK3 expression.publishedVersio

Synthesis, Characterization of Some New Azo Compounds Containing 1,3-Oxazepine, Anthraquinone Moieties and Studying Their Activity against Pathogenic Bacteria

This research includes design of new derivatives for anthraquinone azo compounds bearing 1,3-oxazepine rings with  different saromatic moieties. Diazonium salt of 1-aminoanthraquinone [1] prepared by reaction of 1-aminoanthraquinone with ammonium nitrite in the presence of hydrochloric acid. Then this compound used to prepare of azo derivative [2] through reaction with o-Salicyladehyde. Compound [2] then converted into different Schiff bases [3-8] by treating it with different amino benzenes in absolute ethanol.  Finally 1,3-Oxazepine compounds [9-14] and [15-20] obtained from reaction of Schiff bases [3-8] with phthalic anhydride and maleic anhydride respectively. Physiochemical properties of synthesized compounds determined by their melting points, FTIR, 1HNMR and 13CNMR spectroscopy. The purity and reaction time were checked by TLC. The new prepared 1,3-oxazepine compounds were evaluated against some pathogenic bacteria for their biological activity testing using three different bacterial species including (Klebsiella sp., Streptococcus Pneumonia, Proteus sp.) and compared with (amoxicillin tri hydrate) was used as references drug. The results showed that many of the tested compounds have moderate to good vital activity against the mentioned pathogenic bacteria compared with references drug above. Keywords: Synthesis, Azo compounds, 1,3-Oxazepine , Anthraquinone, Activity.

Families of Women Entrepreneurs in Pakistan Their Paramount Support or Dreadful Obstacle

Purpose: This research aims to identify some female entrepreneurs and their relationship profiles with their families, which are categorized by families having a prominent part in influencing their decisions, activities, and behavior. Methodology: The qualitative technique was used as it is well suited to examining the experiences of different people. Open-ended Interviews with Pakistani female entrepreneurs using a semi-structured questionnaire were used to obtain data. The research allowed us to focus on one of the most pressing concerns affecting female entrepreneurs: integrating life with family, work, and their goals related to their profession. Findings: Evidently, knowing and understanding the importance of the household in the entrepreneurial experiences of women is critical to deciphering the reasons why enterprises that are owned by women thrive or crash, as family relations will invariably influence their performance. Conclusion: The research revealed that female entrepreneurs and their families have a significant linkage with their entrepreneurial experiences i.e., individual decisions of women to become entrepreneurs and the features of their businesses cannot be fully comprehended unless the family dimension is also considered

Synthesis, Characterization and Preliminary Pharmacological Evaluation of Triazolothiadiazoles Derived from some NSAIDs and Thiocarbohydrazide

The synthesis of new NSAIDs with improved efficacy and selectivity towards COX2, which encouraged by the various biological activities of 1,2,4-triazoles and 1,3,4-thiadiazoles. In this experiment, the production of 1,2,4-triazolothiadiazoles derivatives from Ibuprofen, Naproxen and Indomethacin. We have enhanced anti-inflammatory and analgesic activities by conventional method and microwave-assisted technique, and then compare the time consuming by reaction and yield percent of the product in both way, besides evaluation of anti-inflammatory action of the target compounds by pharmacological test with predictable selectivity towards COX-2 enzyme. Synthesis of the target compounds (P1a-3b, N1a-3b and I1a-3b) has been successfully accomplished by checking purity, characterization, also identification of the synthetic compounds which detected by estimation of physical properties, FT-IR and ¹H-NMR spectroscopy. In vivo potent anti-inflammatory activity of the ending compounds are evaluating in rats utilizing egg-white prompted edema model of inflammation. The experienced compounds (P1a-3b, N1a-3b and I1a-3b) and the reference drugs (Ibuprofen, Naproxen and Indomethacin) produced significant reduction in paw edema in compare to the effect of control group. Wholly tested compounds produced considerable decrease of paw edema in contrast to control group. However, compounds (P3b, N3b and I1b) have considerable more paw edema declining than Ibuprofen, Naproxen and Indomethacin. Intermediate and target compounds are synthesis by microwave method have better result by time and yield in compare with conventional way. The synthesized compounds (Pa1-3b and N1a-3b) may exhibit expected selectivity towards COX-2 enzyme properly due to their large size than its parent Ibuprofen, Naproxe

Quantitative transcriptomics, and lipidomics in evaluating ovarian developmental effects in Atlantic cod (Gadus morhua) caged at a capped marine waste disposal site

In the present study, a previously capped waste disposal site at Kollevåg (Norway) was selected to study the effects of contaminant leakage on biomarkers associated with Atlantic cod (Gadus morhua) reproductive endocrinology and development. Immature cod were caged for 6 weeks at 3 locations, selected to achieve a spatial gradient of contamination, and compared to a reference station. Quantitative transcriptomic, and lipidomic analysis was used to evaluate the effects of the potential complex contaminant mixture on ovarian developmental and endocrine physiology. The number of expressed transcripts, with 0.75 log2-fold differential expression or more, varied among stations and paralleled the severity of contamination. Particularly, significant bioaccumulation of ∑PCB-7, ∑DDTs and ∑PBDEs were observed at station 1, compared to the other station, including the reference station. Respectively 1416, 698 and 719 differentially expressed genes (DEGs), were observed at stations 1, 2 and 3, compared to the reference station, with transcripts belonging to steroid hormone synthesis pathway being significantly upregulation. Transcription factors such as esr2 and ahr2 were increased at all three stations, with highest fold-change at Station 1. MetaCore pathway maps identified affected pathways that are involved in ovarian physiology, where some unique pathways were significantly affected at each station. For the lipidomics, sphingolipid metabolism was particularly affected at station 1, and these effects paralleled the high contaminant burden at this station. Overall, our findings showed a novel and direct association between contaminant burden and ovarian toxicological and endocrine physiological responses in cod caged at the capped Kollevåg waste disposal site.publishedVersio

A Very Low Power MAC (VLPM) Protocol for Wireless Body Area Networks

Wireless Body Area Networks (WBANs) consist of a limited number of battery operated nodes that are used to monitor the vital signs of a patient over long periods of time without restricting the patient’s movements. They are an easy and fast way to diagnose the patient’s status and to consult the doctor. Device as well as network lifetime are among the most important factors in a WBAN. Prolonging the lifetime of the WBAN strongly depends on controlling the energy consumption of sensor nodes. To achieve energy efficiency, low duty cycle MAC protocols are used, but for medical applications, especially in the case of pacemakers where data have time-limited relevance, these protocols increase latency which is highly undesirable and leads to system instability. In this paper, we propose a low power MAC protocol (VLPM) based on existing wakeup radio approaches which reduce energy consumption as well as improving the response time of a node. We categorize the traffic into uplink and downlink traffic. The nodes are equipped with both a low power wake-up transmitter and receiver. The low power wake-up receiver monitors the activity on channel all the time with a very low power and keeps the MCU (Micro Controller Unit) along with main radio in sleep mode. When a node [BN or BNC (BAN Coordinator)] wants to communicate with another node, it uses the low-power radio to send a wakeup packet, which will prompt the receiver to power up its primary radio to listen for the message that follows shortly. The wake-up packet contains the desired node’s ID along with some other information to let the targeted node to wake-up and take part in communication and let all other nodes to go to sleep mode quickly. The VLPM protocol is proposed for applications having low traffic conditions. For high traffic rates, optimization is needed. Analytical results show that the proposed protocol outperforms both synchronized and unsynchronized MAC protocols like T-MAC, SCP-MAC, B-MAC and X-MAC in terms of energy consumption and response time

The impact of chronotype on VO2max in university students at two different times of the day

Background and Study Aim. To choose the ideal training or performance times, it is crucial to assess VO2 max performance across different time-of-day particular chronotypes. This study aimed to investigate the differences in VO2 max between the chronotype of university students during the morning and evening time of the day. Material and Methods. Fifty-two university students (26 morning type and 26 evening type) with mean age 23.05± 2.07 years, weight 66.71±4.31Kg and height of 170.90±5.18 cm and BMI of 22.75±1.91kg/m2 were recruited based on the results of the Horne-Ostberg Morningness- Eveningness Questionnaire (MEQs) participated in this Cross-over study. VO2 max was measured directly by gas collected using mouth tube breath to breath through the use of the gas analyzer the AD instrument (model-ML206) with an incremental graded maximal exercise test done on the treadmill. Results. The morning type group's VO2 max was significantly better in the morning hour than it was in the evening (p=.013), and when the VO2 max of the evening type group was measured in the morning and evening hours and compared, there was a statistically significant difference in favour of the evening hours (p=.004). Additionally, there is no discernible difference between the VO2 max of the morning type and the evening type group either in the morning hours or the evening hours, but trends indicate that the morning type group has a higher VO2max in the morning hour and the same is true for the evening type group in the evening hour. Conclusion. The findings of this study showed an interaction between chronotype and time of the day in VO2 max. For endurance training, trainers should consider the individual's chronotype and time of the day for exercise prescription

Modulation of neuro-dopamine homeostasis in juvenile female Atlantic cod (Gadus morhua) exposed to polycyclic aromatic hydrocarbons and perfluoroalkyl substances

The dopaminergic effect of PAH and PFAS mixtures, prepared according to environmentally relevant concentrations, has been studied in juvenile female Atlantic cod (Gadus morhua). Benzo[a]pyrene, dibenzothiophene, fluorene, naphthalene, phenanthrene, and pyrene were used to prepare a PAH mixture, while PFNA, PFOA, PFOS, and PFTrA were used to prepare a PFAS mixture. Cod were injected intraperitoneally twice, with either a low (1×) or high (20×) dose of each compound mixture or their combinations. After 2 weeks of exposure, levels of plasma 17β-estradiol (E2) were significantly elevated in high PAH/high PFAS treated group. Brain dopamine/metabolite ratios (DOPAC/dopamine and HVA+DOPAC/dopamine) changed with E2 plasma levels, except for high PAH/low PFAS and low PAH/high PFAS treated groups. On the transcript levels, th mRNA inversely correlated with dopamine/metabolite ratios and gnrh2 mRNA levels. Respective decreases and increases of drd1 and drd2a after exposure to the high PAH dose were observed. Specifically, high PFAS exposure decreased both drds, leading to high plasma E2 concentrations. Other studied end points suggest that these compounds, at different doses and combinations, have different toxicity threshold and modes of action. These effects indicate potential alterations in the feedback signaling processes within the dopaminergic pathway by these contaminant mixtures.acceptedVersio

Emphysematous cholecystitis with perforation and biliary peritonitis

Emphysematous cholecystitis (EC), uncommon but potentially fatal sequelae of acute cholecystitis mainly seen in old-aged patients with high mortality rate, caused by secondary infection of gall bladder with gas-forming enteric organisms. Herein, we report a case of emphysematous gangrenous cholecystitis with perforation and biliary peritonitis in a 76-years-old non-diabetic lady that was successfully managed by surgical intervention coupled with medical. The report of this case highlights the risk of missing this extremely rare but potentially fatal condition once the patient presents in late-stage with concurrent complications like perforation and peritonitis. Therefore, prompt diagnosis and early surgical intervention is imperative are imperative to avoid undesired outcomes