Antimicrobial potential of alkaloids and flavonoids extracted from Tamarix aphylla leaves against common human pathogenic bacteria

Background: Alkaloids and flavonoids are secondary metabolites extracted from different medicinal plants. Tamarix aphylla a traditionally valuable medicinal plant; was used for the extraction of alkaloids and flavonoids in order to evaluate their antibacterial activity.Methodology: The leaves of the plant were collected from district Kohat, Pakistan, and their alkaloids and flavonoids were extracted with ethanol and methanol, respectively. Four bacteria i.e. Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) were selected for the biological screening of these phyto-constituents.Results: The concentration of alkaloids was found to be more in the leaves of Tamarix aphylla than flavonoids. The extracted phytochemicals showed varied inhibition zones against tested bacterial isolates. Alkaloids showed highest inhibitory activity against Staphylococcus aureus (14±0.6 mm) followed by Pseudomonas aeruginosa (13±0.7 mm). Conversely, flavonoids showed the highest inhibitory affect against Salmonella typhi (17±0.7 mm) followed by Staphylococcus aureus (14±0.7 mm). However, both extracts showed the lowest inhibitory effects against Escherichia coli.Conclusions: It was concluded that the alkaloids and flavonoids from Tamarix aphylla leaves have antimicrobial potential against common human bacterial pathogens. However, flavonoids were found to be more active phytochemical against tested bacterial strains as compared to alkaloids.Keywords: Kohat; Medicinal plants; Phytochemical screening; In-vitro activity; Bacterial strains

Genome wide association study for growth in Pakistani dromedary camels using genotyping-by-sequencing

Objective Growth performance and growth-related traits have a crucial role in livestock due to their influence on productivity. This genome-wide association study (GWAS) in Pakistani dromedary camels was conducted to identify single nucleotide polymorphisms (SNPs) associated with growth at specific camel ages, and for selected SNPs, to investigate in detail how their effects change with increasing camel age. This is the first GWAS conducted on dromedary camels in this region. Methods Two Pakistani breeds, Marecha and Lassi, were selected for this study. A genotyping-by-sequencing method was used, and a total of 65,644 SNPs were identified. For GWAS, weight records data with several body weight traits, namely, birthweight, weaning weight, and weights of camels at 1, 2, 4, and 6 years of age were analysed by using model-based growth curve analysis. Age-specific weight data were analysed with a linear mixed model that included fixed effects of SNP genotype as well as sex. Results Based on the q-value method for false discovery control, for Marecha camels, five SNPs at q<0.01 and 96 at q<0.05 were significantly associated with the weight traits considered, while three (q<0.01) and seven (q<0.05) SNP associations were identified for Lassi camels. Several candidate genes harbouring these SNP were discovered. Conclusion These results will help to better understand the genetic architecture of growth including how these genes are expressed at different phases of their life. This will serve to lay the foundations for applied breeding programs of camels by allowing the genetic selection of superior animals

Volumetric analysis of the piriform cortex in temporal lobe epilepsy

The piriform cortex, at the confluence of the temporal and frontal lobes, generates seizures in response to chemical convulsants and electrical stimulation. Resection of more than 50% of the piriform cortex in anterior temporal lobe resection for refractory temporal lobe epilepsy (TLE) was associated with a 16-fold higher chance of seizure freedom. The objectives of the current study were to implement a robust protocol to measure piriform cortex volumes and to quantify the correlation of these volumes with clinical characteristics of TLE. Sixty individuals with unilateral TLE (33 left) and 20 healthy controls had volumetric analysis of left and right piriform cortex and hippocampi. A protocol for segmenting and measuring the volumes of the piriform cortices was implemented, with good inter-rater and test-retest reliability. The right piriform cortex volume was consistently larger than the left piriform cortex in both healthy controls and patients with TLE. In controls, the mean volume of the right piriform cortex was 17.7% larger than the left, and the right piriform cortex extended a mean of 6 mm (Range: -4 to 12) more anteriorly than the left. This asymmetry was also seen in left and right TLE. In TLE patients overall, the piriform cortices were not significantly smaller than in controls. Hippocampal sclerosis was associated with decreased ipsilateral and contralateral piriform cortex volumes. The piriform cortex volumes, both ipsilateral and contralateral to the epileptic temporal lobe, were smaller with a longer duration of epilepsy. There was no significant association between piriform cortex volumes and the frequency of focal seizures with impaired awareness or the number of anti-seizure medications taken. Implementation of robust segmentation will enable consistent neurosurgical resection in anterior temporal lobe surgery for refractory TLE.

Increased Regional Epicardial Fat Volume Associated with Reversible Myocardial Ischemia in Patients with Suspected Coronary Artery Disease

Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm3, 156.4 ± 121.9 cm3, and 96.3 ± 102.1 cm3, respectively (P < 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm3; P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm3; P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease

Synthesis of 2-{[5-(aralkyl/aryl)-1,3,4-oxadiazol-2- yl]sulfanyl}-N-(4-methyl-1,3-thiazol-2-yl)acetamides: Novel bi-heterocycles as potential therapeutic agents

Purpose: To evaluate the therapeutic potential of new bi-heterocycles  containing a 1,3-thiazole and 1,3,4-oxadiazole in the skeleton against Alzheimer's disease and diabetes, supported by in-silico study. Methods: The synthesis was initiated by the reaction of 4-methyl- 1,3-thiazol-2-amine (1) with bromoacetyl bromide (2) in aqueous basic medium to obtain an electrophile,2-bromo-N-(4-methyl-1,3- thiazol- 2-yl)acetamide (3). In parallel reactions, a series of carboxylic acids, 4a-r, were converted through a sequence of three steps, into respective 1,3,4-oxadiazole heterocyclic cores, 7a-r, to utilize as nucleophiles. Finally, the designed molecules, 8a-r, were synthesized by coupling 7a-r individually with 3 in an aprotic polar solvent. The structures of these bi-heterocycles were elucidated by infrared (IR), electron ionization-mass spectrometry (EI-MS), proton nuclear magnetic resonance (1H-NMR) and carbon nuclear magnetic resonance (13C-NMR). To evaluate their enzyme inhibitory potential, 8a-r were screened against acetylcholinesterase (AChE), but brine shrimp lethality bioassay.Results: The most active compound against AChE was 8l with half-maximal inhibitory concentration (IC50) of 17.25 ± 0.07 μM. Against BChE, the highest inhibitory effect was shown by 8k (56.23 ± 0.09 μM). Compound 8f (161.26 ± 0.23μM) was recognized as a fairly good inhibitor of urease. In view of its inhibition of α-glucosidase, 8o (57.35 ± 0.17μM) was considered a potential therapeutic agent.Conclusion: The results indicate that some of the synthesized products with low toxicity exhibit notable enzyme inhibitory activity against selected enzymes compared with the reference drug, and therefore, are of potential therapeutic interestKeywords: 4-Methyl-1,3-thiazol-2-amine,1,3,4-Oxadiazole,  Cholinesterases, α-Glucosidase, Urease, Brine shrim

First-in-Class Humanized Antibody against Alternatively Spliced Tissue Factor Augments Anti-Metastatic Efficacy of Chemotherapy in a Preclinical Model of Pancreatic Ductal Adenocarcinoma

Alternatively spliced tissue factor (asTF) promotes the progression of pancreatic ductal adenocarcinoma (PDAC) by activating β1-integrins on PDAC cell surfaces. hRabMab1, a first-in-class humanized inhibitory anti-asTF antibody we recently developed, can suppress PDAC primary tumor growth as a single agent. Whether hRabMab1 has the potential to suppress metastases in PDAC is unknown. Following in vivo screening of three asTF-proficient human PDAC cell lines, we chose to make use of KRAS G12V-mutant human PDAC cell line PaCa-44, which yields aggressive primary orthotopic tumors with spontaneous spread to PDAC-relevant anatomical sites, along with concomitant severe leukocytosis. The experimental design featured orthotopic tumors formed by luciferase labeled PaCa-44 cells; administration of hRabMab1 alone or in combination with gemcitabine/paclitaxel (gem/PTX); and the assessment of the treatment outcomes on the primary tumor tissue as well as systemic spread. When administered alone, hRabMab1 exhibited poor penetration of tumor tissue; however, hRabMab1 was abundant in tumor tissue when co-administered with gem/PTX, which resulted in a significant decrease in tumor cell proliferation; leukocyte infiltration; and neovascularization. Gem/PTX alone reduced primary tumor volume, but not metastatic spread; only the combination of hRabMab1 and gem/PTX significantly reduced metastatic spread. RNA-seq analysis of primary tumors showed that the addition of hRabMab1 to gem/PTX enhanced the downregulation of tubulin binding and microtubule motor activity. In the liver, hRabMab1 reduced liver metastasis as a single agent. Only the combination of hRabMab1 and gem/PTX eliminated tumor cell-induced leukocytosis. We here demonstrate for the first time that hRabMab1 may help suppress metastasis in PDAC. hRabMab1’s ability to improve the efficacy of chemotherapy is significant and warrants further investigation

Being tolerated and being discriminated against:Links to psychological well-being through threatened social identity needs

We investigated whether and how the experience of being tolerated and of being discriminated against are associated with psychological well‐being in three correlational studies among three stigmatized groups in Turkey (LGBTI group members, people with disabilities, and ethnic Kurds, total N = 862). Perceived threat to social identity needs (esteem, meaning, belonging, efficacy, and continuity) was examined as a mediator in these associations. Structural equation models showed evidence for the detrimental role of both toleration and discrimination experiences on positive and negative psychological well‐being through higher levels of threatened social identity needs. A mini‐meta analysis showed small to moderate effect sizes and toleration was associated with lower positive well‐being through threatened needs among all three stigmatized groups

Smart Grid, Demand Response and Optimization: A Critical Review of Computational Methods

In view of scarcity of traditional energy resources and environmental issues, renewable energy resources (RERs) are introduced to fulfill the electricity requirement of growing world. Moreover, the effective utilization of RERs to fulfill the varying electricity demands of customers can be achieved via demand response (DR). Furthermore, control techniques, decision variables and offered motivations are the ways to introduce DR into distribution network (DN). This categorization needs to be optimized to balance the supply and demand in DN. Therefore, intelligent algorithms are employed to achieve optimized DR. However, these algorithms are computationally restrained to handle the parametric load of uncertainty involved with RERs and power system. Henceforth, this paper focuses on the limitations of intelligent algorithms for DR. Furthermore, a comparative study of different intelligent algorithms for DR is discussed. Based on conclusions, quantum algorithms are recommended to optimize the computational burden for DR in future smart grid