Revisiting Plant Heterosis-From Field Scale to Molecules.

Heterosis refers to the increase in biomass, stature, fertility, and other characters that impart superior performance to the F1 progeny over genetically diverged parents. The manifestation of heterosis brought an economic revolution to the agricultural production and seed sector in the last few decades. Initially, the idea was exploited in cross-pollinated plants, but eventually acquired serious attention in self-pollinated crops as well. Regardless of harvesting the benefits of heterosis, a century-long discussion is continued to understand the underlying basis of this phenomenon. The massive increase in knowledge of various fields of science such as genetics, epigenetics, genomics, proteomics, and metabolomics persistently provide new insights to understand the reasons for the expression of hybrid vigor. In this review, we have gathered information ranging from classical genetic studies, field experiments to various high-throughput omics and computational modelling studies in order to understand the underlying basis of heterosis. The modern-day science has worked significantly to pull off our understanding of heterosis yet leaving open questions that requires further research and experimentation. Answering these questions would possibly equip today's plant breeders with efficient tools and accurate choices to breed crops for a sustainable future.

Pd(II) complexes with chelating N-(1-alkylpyridin-4(1H)-ylidene)amide (PYA) ligands: Synthesis, characterization and evaluation of anticancer activity.

The bidentate N-(1-Alkylpyridin-4(1H)-ylidene)amide (PYA) pro-ligands [H2LBn][Cl]2 (2), and [H2LMe][TfO]2 (3) were prepared by simple alkylation reactions of the known compound, N,N-di(pyridin-4-yl)oxalamide (H2L, 1). The Pd(II) complexes, [Pd(LBn)2][Cl]2 (4), [Pd(LMe)2][Cl][TfO] (5), Pd(LBn)Cl2 (6) and Pd(LMe)Cl2 (7) were synthesized through reactions between these pro-ligands and suitable Pd(II) substrates in the presence of base. The molecular structures of 3 and 6 were obtained by single crystal X-ray structure determinations. Studies of the experimental and computational DNA binding interactions of the compounds 1-7 revealed that overall 4 and 6 have the largest values for the binding parameters Kb and ΔGbo. The results showed a good correlation with the steric and electronic parameters obtained by quantitative structure activity relationship (QSAR) studies. In-vitro cytotoxicity studies against four different cell lines showed that the human breast cancer cell lines MCF-7, T47D and cervical cancer cell line HeLa had either higher or similar sensitivities towards 4, 6 and 2, respectively, compared to cisplatin. In general, the cytotoxicity of the compounds, represented by IC50 values, decreased in the order 4 > 6 > 2 > 5 > 3 > 1 > 7 in cancer cell lines. Apoptosis contributed significantly to the cytotoxic effects of these anticancer agents as evaluated by apoptosis studies.

Investigation of the anti-hyperglycemic and antioxidant effects of wheat bread supplemented with onion peel extract and onion powder in diabetic rats.

AIM: Onion is one of the commonly cultivated and consumed vegetables rich in nutrients and phytochemicals. Various nutraceuticals are found in the outer fleshy layers and dry peel of onion which usually is treated as a common biowaste. Diabetes mellitus is a leading non communicable disease causing hyperglycemia and increased production of free radicals that potentially disrupts antioxidant enzymatic activity. Considering global consumption of wheat, the present study was designed to evaluate the anti-hyperglycemic and antioxidant effects of wheat bread supplemented with onion peel extract (OPE) or onion powder (OP) on diabetic rats. METHODS: In this study, ethanolic extract of onion peel and onion bulb were prepared separately. Male Sprague Dawley rats were divided into 6 groups (n = 7). Different regimens of supplemented wheat bread (OPE (1% and 3%) and OP (5% and 7%)) were given to diabetic rats for eight weeks, plain bread was used as the control. Blood glucose level, body weight and activities of SOD, CAT, GPx, GR, GSH and MDA in the liver and kidney tissues were evaluated. Statistical analysis was performed using SPSS Version (25) and Dunnett's multiple comparison test. RESULTS: Bread supplemented with 1% and 3% onion peel extract and 7% onion powder significantly reduced blood glucose levels and MDA in the treated rats compared with the control group diabetic rats. Body weight of diabetic rats was reduced for control group, while onion supplemented diet improved the body weight of treated rats. Onion supplementation also brought significant improvement in antioxidant enzyme activities among the treated diabetic rats. CONCLUSION: These findings suggested that onion supplementation is effective in lowering blood glucose and could potentially aid in protecting organs from oxidative stress.

Primary lung intravascular large B-Cell lymphoma clinically mimicking sarcoidosis: A rare case report and review of literature.

We present a case of a 73-year-old male who initially presented with night sweats, intermittent fever, worsening dry cough and shortness of breath. CT scans revealed atelectasis and calcified mediastinal lymphadenopathy, raising a suspicion for sarcoidosis. Multiple lung biopsies were performed. Microscopically, atypical lymphocytes were identified within capillaries, small arteries and veins. These lymphocytes were large with prominent nucleoli. Immunohistochemical staining demonstrated tumor cells positive for CD20, CD79a, Pax-5, CD10 and Mum-1, while negative for CD3, cytokeratin, S100, and CD34. LDH serum level was increased (480 IU/L). Extra pulmonary lymphoma was not detected elsewhere in the patient. These findings support the diagnosis of primary lung intravascular large B cell lymphoma (IVLBCL). Literature review of 52 cases demonstrated occurrence of primary lung IVBCL in patients between the ages (35-85) with a slight male predominance (1.167:1). The most common clinical presentation was fever associated with dyspnea.

Synthesis, characterization and anti-cancer properties of water-soluble bis(PYE) pro-ligands and derived palladium(ii) complexes.

The two cationic palladium(ii) complexes, [Pd(Len)2][OTf]2 (4) and [Pd(Lphen)2][OTf]2 (5), were synthesized by treatment of bis(benzonitrile)dichloropalladium(ii) with [H2Len][OTf]2 (2) or [H2Lphen][OTf]2 (3), respectively, in the presence of a weak base. The pro-ligands 2 and 3 were synthesized by melt reactions between N-methyl-4-chloropyridinium triflate (1) and the amines ethylenediamine or phenylenediamine, respectively. The water-soluble compounds 2-5 were fully characterized, including by single-crystal X-ray crystal structure determinations for 2-4. UV-Vis and fluorescence spectroscopy were used to study the binding interactions of 2-5 with CT-DNA. The spectroscopic data suggested the presence of intercalative and groove binding modes and this was supported by molecular docking studies. The in vitro cytotoxicity studies (IC50 values) showed that the human breast cancer cell lines MCF-7 and T47D were more sensitive towards 3, 4 and 5 than cisplatin. The cytotoxicity of the new compounds decreased in the order 5 > 4 > 3 > 2. Furthermore, the annexin V-FITC staining method strongly suggested the presence of phosphatidylserine (PS) on the outer membrane of the treated cells, which is a hallmark of apoptosis.

Anti-malarial, cytotoxicity and molecular docking studies of quinolinyl chalcones as potential anti-malarial agent.

The quinolinyl chalcones series (A1-A14) were screened for antimalarial activity. According to in vitro antimalarial studies, many quinolinyl chalcones are potentially active against CQ-sensitive and resistance P. falciparum strains with no toxicity against Vero cell lines. The most active quinolinyl chalcones A4 (with IC50 0.031 µM) made a stable A4-heme complex with - 25 kcal/mole binding energy and also showed strong π-π interaction at 3.5 Å. Thus, the stable A4-heme complex formation suggested that these quinolinyl chalcones act as a blocker for heme polymerization. The docking results of quinolinyl chalcones with Pf-DHFR showed that the halogenated benzene part of quinolinyl chalcones made strong interaction with Pf-DHFR as compared to quinoline part. A strong A4-Pf-DHFR complex was formed with low binding energy (- 11.04 kcal/mole). The ADMET properties of quinolinyl chalcones were also studied. The in vivo antimalarial studies also confirmed the A4 as an active antimalarial agent.

Synthesis of new Pro-PYE ligands as co-catalysts toward Pd-catalyzed Heck-Mizoroki cross coupling reactions.

The present research work describes the synthesis of five new ligands containing pyridinium amine, [H2L1][OTf]2-[H2L5][I]2 from two new precursors, [P3 Et][I] and [P2 Me][CF3SO3]. The structure elucidations of the compounds were confirmed by multinuclear NMR (1H, 13C), FT-IR and by single crystal XRD techniques. Theoretical DFT studies were carried out to get better insight into the electronic levels and structural features of all the molecules. These synthesized new Pro-PYE ligands [H2L1][OTf]2-[H2L5][I]2 were found to be significantly active as co-catalysts for Pd(CH3CO2)2 toward Heck-Mizoroki coupling reactions with wide substrate scope in the order of [H2L1][OTf]2 ≫ [H2L2][OTf]2 > [H2L3][OTf]2 > [H2L4][OTf]2 > [H2L5][I]2.

Anti-HIV cytotoxicity enzyme inhibition and molecular docking studies of quinoline based chalcones as potential non-nucleoside reverse transcriptase inhibitors (NNRT).

A series of fourteen (A1 - A14) qunioline based chalcones were screened for reverse transcriptase inhibitors (RT) and found potentially active against RT. Bioassay, theoretical and dockings studies with RT (the enzyme required for reverse transcription of viral RNA) results showed that the type and positions of the substituents seemed to be critical for their inhibition against RT. The bromo and chloro substituted chalcone displayed high degree of inhibition against RT. The A4 andA6 showed high interaction with RT, contributing high free binding energy (ΔG -9.30 and -9.13kcal) and RT inhibition value (IC50 0.10µg/ml and 0.11µg/ml).

Pseudomonas aeruginosa ExoT Induces Mitochondrial Apoptosis in Target Host Cells in a Manner That Depends on Its GTPase-activating Protein (GAP) Domain Activity.

Pseudomonas aeruginosa is the most common cause of hospital-acquired pneumonia and a killer of immunocompromised patients. We and others have demonstrated that the type III secretion system (T3SS) effector protein ExoT plays a pivotal role in facilitating P. aeruginosa pathogenesis. ExoT possesses an N-terminal GTPase-activating protein (GAP) domain and a C-terminal ADP-ribosyltransferase (ADPRT) domain. Because it targets multiple non-overlapping cellular targets, ExoT performs several distinct virulence functions for P. aeruginosa, including induction of apoptosis in a variety of target host cells. Both the ADPRT and the GAP domain activities contribute to ExoT-induced apoptosis. The ADPRT domain of ExoT induces atypical anoikis by transforming an innocuous cellular protein, Crk, into a cytotoxin, which interferes with integrin survival signaling. However, the mechanism underlying the GAP-induced apoptosis remains unknown. In this study, we demonstrate that the GAP domain activity is both necessary and sufficient to induce mitochondrial (intrinsic) apoptosis. We show that intoxication with GAP domain results in: (i) JNK1/2 activation; (ii) substantial increases in the mitochondrial levels of activated pro-apoptotic proteins Bax and Bid, and to a lesser extent Bim; (iii) loss of mitochondrial membrane potential and cytochrome c release; and (iv) activation of initiator caspase-9 and executioner caspase-3. Further, GAP-induced apoptosis is partially mediated by JNK1/2, but it is completely dependent on caspase-9 activity. Together, the ADPRT and the GAP domains make ExoT into a highly versatile and potent cytotoxin, capable of inducing multiple forms of apoptosis in target host cells.

Synthesis, characterization, theoretical, anti-bacterial and molecular docking studies of quinoline based chalcones as a DNA gyrase inhibitor.

A series of fourteen (A1-A14) new qunioline based chalcones were synthesized by condensing 2,7-dichloro-8-methyl-3-formyl quinoline with acetophenone and acetylthiophenes, and subsequently characterized by IR, NMR and Mass spectroscopy. All the compounds were screened for antibacterial activities and found potentially active antibacterial agents. Bioassay, theoretical and dockings studies with DNA gyrase (the enzyme required for super coiling of DNA of bacteria) results showed that the type and positions of the substituents seemed to be critical for their antibacterial activities. The bromo and chloro substituted chalcone displayed high anti-bacterial activity. The A4 and A6 showed high interaction with DNA gyrase, contributing high free binding energy (ΔG -8.18 and -8.88 kcal).

Current understanding of treatment and management protocol for adult diabetic in-patients at a tertiary care hospital.

OBJECTIVE: To assess the current understanding of treatment and management protocols for adult diabetic inpatients at a tertiary care hospital. METHODS: This cross-sectional study, conducted at the Civil Hospital Karachi from July to September 2009, involved 450 participants, who were interviewed through a well-structured questionnaire regarding the patient's demography, clinical features, past medical history, type of diabetes mellitus, duration, associated complications, and also involved patient notes for laboratory tests and management. SPSSv15.0 was used for descriptive analysis. RESULTS: The study population of 450 diabetics had 144 (32%) males and 306 (68%) females. Of the total, 435 (96.7%) patients had type 2 diabetes. There were 231 (51%) patients using insulin, 168 (37.3%) oral hypoglycaemic drugs, and 51 (11.3%) using both. Among patients using insulin, regular insulin usage stood at 30% followed by a combination of regular insulin and NPH (26.7%) and NPH alone at 6%. The most popular drug used was metformin (27.3%) and the least used drug was glitazones (4%). In the study population, 73.3% patients controlled their diabetes with diet, and 24.7% with regular exercise. CONCLUSION: Majority of the study population had type 2 diabetes with a female preponderance. Insulin was prescribed for half the patients. Metformin was the most frequently used oral hypoglycaemic drug.

Factors predicting the recurrence of spontaneous bacterial peritonitis in patients with cirrhosis.

OBJECTIVE: To evaluate the frequency of recurrence of spontaneous bacterial peritonitis (SBP) in patients with end stage liver disease and the factors responsible for it. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from November 2008 till November 2009. METHODOLOGY: Patients with cirrhosis who were admitted at AKUH with diagnosis of SBP during the study period were included. Any episode of SBP after resolution of the first index case of SBP within one year was considered as recurrence. RESULTS: Out of 238 cirrhotic patients, 157 (66%) had single, while 81 (34%) had recurrent episodes of SBP. History of using proton pump inhibitors (PPI) and diuretics was found in 113 (47.5%) and 139 (58.4%) patients respectively. Only 58 24.4%) patients were on prophylactic antibiotic therapy. Univariate analysis revealed that the female gender (52%), and presence of porto-systemic encephalopathy (PSE, 31%) were statistically significant (p=0.03) among those who had recurrent SBP. On multivariate analysis bilirubin level of > 1.0 mg (OR=7.03; 95%CI=1.55-32), protective factor of hepatitis B (OR 0.31; 95%CI=0.13-0.70) and presence of urinary tract infection (UTI) (OR=2.24; 95%CI=0.99-5.09) were significant in patients with recurrent SBP. CONCLUSION: Recurrent SBP was noticed in 34% patients. Serum bilirubin level of > 1.0 mg, protective factor of HBV and presence of UTI were significant factors present in patients with recurrent SBP.

Frequency of infectious skin lesions in kidney transplant recipients.

INTRODUCTION: This study was performed to evaluate the frequency of skin lesions in kidney transplant recipients. MATERIALS AND METHODS: A total of 681 kidney transplant recipients were followed at Shaheed Labbafinejad transplant center in Tehran, Iran. Skin lesions were evaluated, and diagnoses were made clinically and confirmed by lesion smear, tissue biopsy, tissue culture, and serologic examinations, as indicated. RESULTS: Skin lesions were found in 54 patients (7.9%), and their frequencies were as follows: dermatomal herpes zoster (18 patients, 2.6%, 13 men and 5 women), herpes simplex infection of face and lips (15 patients, 2.2%, 5 men and 10 women), chickenpox (6 patients, 0.9%, 5 men and 1 woman), Kaposi's sarcoma (5 patients, 0.7%, 3 men and 2 women), warts (4 women, 2 of whom had genital warts), pyoderma gangrenosum (1 man, 0.14%), multiple fungal abscesses of the leg (1 man, 0.14%), mucormycosis (1 man, 0.14%), and molluscum contagiosum (1 man, 0.14%). Moreover, 2 women (0.3%) had generalized herpes simplex lesions. CONCLUSION: Frequencies of herpes zoster (3.5%), herpes simplex (2.5%), and human papillomavirus (0.6%) infections in our kidney transplant recipients were low. We recommend that all kidney transplant candidates be evaluated and immunized for herpes zoster virus before transplantation, all herpetic-form lesions of these patients be reported to physicians (even mild lesions), and finally, that all human papillomavirus lesions be diagnosed and treated promptly to prevent more serious lesions such as malignancies.