Molecular diversity in rice blast resistance gene Pi-ta makes it highly effective against dynamic population of Magnaporthe oryzae.

Rice blast is one of the important diseases of rice which can be effectively managed by the deployment of resistance genes. Pi-ta is one of the major blast resistant genes effective against pathogen populations in different parts of India. We analysed allelic variants of Pi-ta from 48 rice lines selected after phenotyping of 529 rice landraces across three eco-geographical blast hot spot regions. Besides, Pi-ta orthologue sequences of 220 rice accessions belonging to wild and cultivated species of rice were also included in the study for a better evo-devo perspective of the diversity present in the gene and the selection pressures acting on this locus. We obtained high nucleotide variations (SNPs and insertion-deletions) in the intronic region. We also identified 64 haplotypes based on nucleotide polymorphism in these alleles. Pi-ta orthologues of Indian landraces were scattered in eight major haplotypes indicating its heterogenous nature. We identified a total of 47 different Pi-ta protein variants on the basis of deduced amino acid residues amongst the orthologues. Five unique and novel Pi-ta variants were identified for the first time in rice landraces exhibiting different reaction types against the Magnaporthe oryzae population. A high value of Pi(non/syn) was observed only in the leucine-rich domain of the alleles cloned from Indian landraces, indicating strong selective forces acting on this region. The detailed molecular analysis of the Pi-ta orthologues provides insights to a high degree of inter- and intraspecific relationships amongst the Oryza species. We identified rice landraces possessing the effective alleles of this resistance gene which can be used in future blast resistance breeding programmes.

A new species of Xestophrys Redtenbacher, 1891 (Orthoptera: Tettigoniidae; Conocephalinae; Copiphorini) from West Bengal, India.

A new species, Xestophrys bengalensis sp. nov., from the West Bengal state of India is described in this paper. The new species is superficially similar to the Indonesian species Xestophrys javanicus lombockensis Carl, 1908, but differs from the latter in the smaller size, anterior femur unarmed on the external margin, and hind femur with two spines on the internal margin. A key to the species of Xestophrys Redtenbacher, 1891 is also provided.

A new species of Euconocephalus Karny, 1907 (Orthoptera: Tettigoniidae: Conocephalinae: Copiphorini) from India.

A new species, Euconocephalus narayanpurensis Kumar & Chand sp. nov., from India is described in this paper. The new species is similar to the African species Euconocephalus lineatipes (Bolívar, 1890), but differs from the latter in the smaller size, more acute humeral sinus, the narrowly rounded apex of elytra and convex male last abdominal tergite. A key to the Indian species of Euconocephalus Karny, 1907 is also provided.

Diagnostic tools in coronavirus disease 2019 associated mucormycosis - do we need three-dimensional computed tomography?

OBJECTIVE: Three-dimensional computed tomography reconstruction of the face has recently been presented as a newer diagnostic tool in coronavirus disease 2019 associated mucormycosis. This study was conducted to compare three-dimensional computed tomography reconstruction with conventional two-dimensional computed tomography in coronavirus disease 2019 associated mucormycosis. METHODS: A total of 123 mucormycosis patients underwent three-dimensional computed tomography reconstruction after a comprehensive clinical investigation. The involvement of the facial skeleton was noted. RESULTS: The anterior maxillary wall was most commonly involved (9.8 per cent). Involvement of the lateral maxillary wall was noted in 6.5 per cent of patients. Sixty-seven patients (54.5 per cent) underwent endoscopic surgery, 22 (17.9 per cent) underwent open surgical procedures, and 12 (9.8 per cent) had combined endoscopic and open surgical procedures. In 21 patients (17.1 per cent), open surgery was performed in the first instance based on additional three-dimensional computed tomography findings, and revision surgical procedures were avoided. CONCLUSION: Three-dimensional computed tomography of the face was found to be superior in determining the extent of disease. It reduces delays in diagnosis, facilitates surgical planning and minimises the need for multiple surgical procedures.

Rediscovery of Liara (Unalianus) heteracanthus (Redtenbacher, 1891) (Orthoptera: Tettigoniidae: Conocephalinae: Agraeciini) from India with notes on its distribution.

More than one hundred years after its description, a male specimen of Liara(Unalianus)heteracanthus(Redtenbacher, 1891) was collected at a new locality in the Mizoram State, India. Opportunity is taken to redescribe and illustrate this specimen.

The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry.

PURPOSE: Well-functioning vascular access is essential for the provision of adequate CRRT. However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population. METHODS: Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model. RESULTS: Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001). CONCLUSIONS: Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.

PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib.

Recently, germline and somatic heterozygous mutations in the platelet-derived growth factor receptor ß (PDGFRB) have been associated with familial infantile myofibromatosis (IM), which is characterized by soft tissue tumors, and overgrowth syndrome, a disease that predisposes to cancer. These mutations have not been functionally characterized. In the present study, the activity of three PDGFRB mutants associated with familial IM (R561C, P660T and N666K) and one PDGFRB mutant found in patients with overgrowth syndrome (P584R) was tested in various models. The P660T mutant showed no difference with the wild-type receptor, suggesting that it might represent a polymorphic variant unrelated to the disease. By contrast, the three other mutants were constitutively active and able to transform NIH3T3 and Ba/F3 cells to different extents. In particular, the germline mutant identified in overgrowth syndrome, P584R, was a stronger oncogene than the germline R561C mutant associated with myofibromatosis. The distinct phenotypes associated with these two mutations could be related to this difference of potency. Importantly, all activated mutants were sensitive to tyrosine kinase inhibitors such as imatinib, nilotinib and ponatinib. In conclusion, the PDGFRB mutations previously identified in familial IM and overgrowth syndrome activate the receptor in the absence of ligand, supporting the hypothesis that these mutations cause the diseases. Moreover, imatinib seems to be a promising treatment for patients carrying these mutations. To our knowledge, these are the first confirmed gain-of-function point mutations of PDGFRB in human cancer.

The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN.

The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer. However, in neuroblastoma, activating mutations in the ALK kinase domain are typically refractory to crizotinib treatment, highlighting the need for more potent inhibitors. The next-generation ALK inhibitor PF-06463922 is predicted to exhibit increased affinity for ALK mutants prevalent in neuroblastoma. We examined PF-06463922 activity in ALK-driven neuroblastoma models in vitro and in vivo In vitro kinase assays and cell-based experiments examining ALK mutations of increasing potency show that PF-06463922 is an effective inhibitor of ALK with greater activity towards ALK neuroblastoma mutants. In contrast to crizotinib, single agent administration of PF-06463922 caused dramatic tumor inhibition in both subcutaneous and orthotopic xenografts as well as a mouse model of high-risk neuroblastoma driven by Th-ALK(F1174L)/MYCN Taken together, our results suggest PF-06463922 is a potent inhibitor of crizotinib-resistant ALK mutations, and highlights an important new treatment option for neuroblastoma patients.

Long-term changes in brain cholinergic system and behavior in rats following gestational exposure to lead: protective effect of calcium supplement.

Our earlier studies showed that lactational exposure to lead (Pb) caused irreversible neurochemical alterations in rats. The present study was carried out to examine whether gestational exposure to Pb can cause long-term changes in the brain cholinergic system and behavior of rats. The protective effect of calcium (Ca) supplementation against Pb toxicity was also examined. Pregnant rats were exposed to 0.2% Pb (Pb acetate in drinking water) from gestational day (GD) 6 to GD 21. The results showed decrease in body weight gain (GD 6-21) of dams, whereas no changes were observed in offspring body weight at different postnatal days following Pb exposure. Male offspring treated with Pb showed marginal alterations in developmental landmarks such as unfolding of pinnae, lower and upper incisor eruption, fur development, eye slit formation and eye opening on postnatal day (PND) 1, whereas significant alterations were found in the righting reflex (PNDs 4-7), slant board behavior (PNDs 8-10) and forelimb hang performance (PNDs 12-16). Biochemical analysis showed decrease in synaptosomal acetylcholinesterase (AChE) activity and an increase in acetylcholine (ACh) levels in the cortex, cerebellum and hippocampus on PND 14, PND 21, PND 28 and in the four-month age group of rats following Pb exposure. Significant deficits were also observed in total locomotor activity, exploratory behavior and open field behavior in selected age groups of Pb-exposed rats. These alterations were found to be maximal on PND 28, corresponding with the greater blood lead levels observed on PND 28. Addition of 0.02% Ca to Pb reversed the Pb-induced impairments in the cholinergic system as well as in behavioral parameters of rats. In conclusion, these data suggest that gestational exposure to Pb is able to induce long-term changes in neurological functions of offspring. Maternal Ca administration reversed these neurological effects of Pb later in life, suggesting a protective effect of calcium in Pb-exposed animals.

Hemolytic uremic syndrome in an adolescent with Fusobacterium necrophorum bacteremia.

Microorganisms may produce substances that disrupt the interaction between platelets and vascular endothelium, which has been associated with atypical hemolytic uremic syndrome (HUS). We present the first reported case of Fusobacterium necrophorum bacteremia that presented initially with atypical HUS. Antimicrobial therapy eradicated the patient's bacteremia, and plasmapheresis restored platelet-endothelial homeostasis. Understanding the pathophysiologic mechanisms involved in atypical HUS would guide the development of more precise therapies.

Self-assembly of a novel macrotricyclic Pd(II) metallocage encapsulating a nitrate ion.

Complexation of the ligand 1 with Pd(NO3)2 leads to the self-assembly of a very stable M2L4 type macrotricyclic cage that encapsulates a nitrate ion inside its cavity.

A sensitive and relevant model for evaluating anti-inflammatory activity-papaya latex-induced rat paw inflammation.

A new model employing latex of papaya as an inflammagen has been developed for testing anti-inflammatory activity. The latex (exudate) was harvested from the unripe papaya fruit, which had been dried under vacuum. The latex was then suspended in 0.05 M sodium acetate buffer. This suspension when injected in rat hind paw produced concentration-dependent inflammation. Of the 0.25% of this suspension, 0.1 ml was found ideal for evaluating anti-inflammatory activity of test drugs. This concentration produced 70%-100% inflammation lasting for about 5 hr with a maximum effect at h 3. The test drugs employed were prednisolone, aspirin, indomethacin, phenylbutazone, ibuprofen, piroxicam, chloroquine, levamisole, and a mixture of boswellic acids. For comparison, these drugs were also tested against carrageenan-induced inflammation. All the test drugs--steroidal, aspirin, and non-aspirin-like--showed anti-inflammatory activity against latex-induced inflammation. The activity of chloroquine, levamisole, and boswellic acids was significantly more against latex as compared with that of the carrageenan model. The inflammation caused by latex may be attributed to both its hydrolytic enzymes--papain and chymopapain--and glutathione, the activator of these enzymes. These enzymes seem to act like lysosomal enzymes that are released in inflammatory disease processes which mediate inflammation by stimulating the synthesis of prostaglandins. The papaya latex-induced inflammation model appears to be a sensitive, broad-based, and relevant one likely to prove useful for discovering new and effective drugs against inflammation and rheumatoid arthritis.

Application of papaya latex-induced rat paw inflammation: model for evaluation of slowly acting antiarthritic drugs.

Papaya latex-induced rat paw inflammation model for evaluating antiinflammatory activity has been developed and reported earlier. A number of drugs viz. aspirin, indomethacin, piroxicam, ibuprofen, prednisolone, levamisole, chloroquine, and boswellic acids showed antiinflammatory activity in this model. As the last three drugs showing the activity belonged to the group of slowly acting antiarthritic drugs, this present study was undertaken to study in detail the sensitivity of this model for slowly acting, clinically effective, antiarthritic drugs viz. chloroquine, levamisole, penicillamine, aurothioglucose, cyclophosphamide, and boswellic acids. These drugs are known to show no appreciable activity in the known models of inflammation and arthritis. All these drugs tested in three graded doses showed dose-related significant antiinflammatory activity in this model, whereas those drugs in the carrageenan model tested in similar doses showed insignificant activity. Aspirin employed as a reference standard showed significant activity in both the models. Thus the slowly acting antiarthritic drugs will be identified as those displaying significant activity in the papaya latex model and insignificant activity in the carrageenan model and to be aspirin-like by their significant activity in both the above models of inflammation.

Oxidative stress on lens and cataract formation: role of light and oxygen.

The mechanism of oxidative damage to the lens through intraocular photochemical generation of superoxide and its derivatization to other oxidants such as singlet oxygen, hydroxyl radical and hydrogen peroxide has been studied. Rat lenses when organ cultured aerobically in TC 199 containing additional amounts of riboflavin were damaged as demonstrated by an inhibition of the uptake of Rb 86 against a concentration gradient. The pump was not affected by light if the culture was conducted in the basal TC 199. However, light was observed to induce significant peroxidative degradation of the tissue lipids even in the basal medium, the degradation being indicated by the formation of malonaldehyde. Both the inhibition of the pump as well as the peroxidative degradation of the tissue lipids, were attenuated considerably by scavengers of superoxide and hydrogen peroxide. In addition, the lipid degradation was prevented by vitamins C and E. The results suggest that the photodynamic injury to the lens cation pump as well as to membrane lipids is incumbent upon an initial generation of superoxide and its derivatization to other oxidants. Thus, the ocular lens is susceptible to oxidative insult and physiological damage through photocatalytic generation of various oxygen radicals. Large concentrations of ascorbic acid in the aqueous humor seems to be able to provide significant protection against such an insult. Thus, this may be one of the functions of high concentration of ascorbic acid in the aqueous humor. The implication of oxidative stress has also been examined in the genesis of cataracts in vivo. Treatment with vitamin E of the Emory mouse led to a decrease in the rate of cataract progression suggesting that at least in some instances an oxidative stress could participate in the formation of cataracts. Oxygen radicals may inflict damage at multifarious biochemical sites. Human lens lipids were also shown to have an absorption maxima at 239 nm indicating their susceptibility to oxidative degradation. In addition the lipid extract has fluorescence similar to that of lipofuscins. The levels of MDA were higher in the brunescent cataracts as compared to that in the nonbrunescent cataracts. The implications of oxidative stress towards the genesis of cataracts in humans is being explored further.

Effect of Zizyphus sativa leaves on blood glucose levels in normal and alloxan-diabetic rats.

An alcoholic extract of Zizyphus sativa leaves was tested for hypoglycemic activity in normal and alloxan-diabetic rats. Single (100-400 mg/kg) oral doses of extract to normal animals showed a dose-dependent statistically significant lowering of blood glucose 2, 4 and 6 h later. The effect was most pronounced at 6 h with blood glucose returning to control values at 24 h. In alloxan-diabetic rats, no significant effect was observed with extract and tolbutamide. The minimum lethal dose was greater than 3000 mg/kg, orally in mice.

Comparison of quality and freezability of water buffalo semen after washing or Sephadex filtration.

Split aliquots of pooled buffalo semen samples were processed before freezing 1) by washing twice with Tris-citric acid buffer by centrifugation and re-suspension to the original volume in the same buffer, or 2) or by passage through a G-15 Sephadex column. The effect of these procedures on progressive motility, percentages of live spermatozoa, sperm abnormalities and intact acrosomes and release of glutamate oxatoacetate transaminase (GOT) into the medium were assessed after extension, after equilibration and after 18 to 24 h or 15 d of frozen storage. Prior to extension, gel filtration reduced sperm concentration and enhanced progressive motility, whereas washing produced little effect on these attributes. Except in the case of GOT release, which was significantly (P < 0.05) lower after the washing of semen (34.3 +/- 16.40) than the filtering of semen (45.7 +/- 12.35), the 2 procedures did not cause significant effects (P > 0.05). Damage to spermatozoa due to freeze-processing was also similar in the 2 treatments, and the extent of beneficial effect in improved motility and live spermatozoan numbers after thawing was also similar.

Effect of vitamin E on lipid peroxidation in buffalo Bubalus bubalis L.

Vitamin E significantly (P less than 0.01), inhibited lipid peroxidation as indicated by malonaldehyde (MDA) production and improved significantly (P less than 0.01) motility and percent live spermatazoa of B. bubalis semen. Bulls with higher MDA formation had lower sperm motility and percent live count. Variance due to bulls for all the three parameters were significant (P less than 0.05).

Lipid peroxidation in buffalo (Bubalus bubalis L.) spermatozoa: effect of added vitamin C and glucose.

Addition of 2.5 mM vitamin C or 40 mM of glucose to washed buffalo spermatozoan suspensions in Ca2(+)-free Kreb's Ringer Hanseliet saline buffer (pH 7.0) resulted in significant lower malonaldehyde concentration and higher spermatozoan motility and liver spermatozoa compared to control levels after 45 min of aerobic incubation at 37 degrees C or pre-incubation levels.

PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations.

Activating mutations in the platelet-derived growth factor (PDGF) receptor alpha (PDGFRA) have been described in patients with gastrointestinal stromal tumors or myeloid malignancies associated with hypereosinophilia. These patients respond well to imatinib mesylate, raising the question as to whether patients with a PDGF receptor mutation in other tumor types should receive a tyrosine kinase inhibitor treatment. We characterized 10 novel somatic point mutations in PDGFRA that have been reported in isolated cases of glioblastoma, melanoma, acute myeloid leukemia, peripheral nerve sheath tumors and neuroendocrine carcinoma. The PDGFRA transmembrane domain mutation V536E stimulated Ba/F3 cell growth and signaling via ERK and STAT5 in the absence of ligand. This mutant, identified in glioblastoma, was strongly inhibited by imatinib. Modeling suggested that the mutation modulates the packing of the transmembrane domain helices in the receptor dimer. By contrast, two mutations in highly conserved residues affected the receptor traffic to the cell surface or kinase activity, thereby preventing the response to PDGF. The other mutations had no significant impact on the receptor activity. This functional analysis matched the predictions of SIFT and PolyPhen for only five mutations and these algorithms do not discriminate gain from loss of function. Finally, an E996K variant that had been identified in a melanoma cell line was not expressed in these cells. Altogether, several newly identified PDGFRA mutations do not activate the receptor and may therefore represent passenger mutations. Our results also underline the importance of characterizing novel kinase alterations in cancer patients.

C-Terminal region of teneurin-1 co-localizes with dystroglycan and modulates cytoskeletal organization through an extracellular signal-regulated kinase-dependent stathmin- and filamin A-mediated mechanism in hippocampal cells.

The pyramidal neurons in the hippocampus are extremely neuroplastic, and the complexity of dendritic branches can be dynamically altered in response to a variety of stimuli, including learning and stress. Recently, the teneurin family of proteins has emerged as an interneuronal and extracellular matrix signaling system that plays a significant role in brain development and neuronal communication. Encoded on the last exon of the teneurin genes is a new family of bioactive peptides termed the teneurin C-terminal-associated peptides (TCAPs). Previous studies indicate that TCAP-1 regulates axon fasciculation and dendritic morphology in the hippocampus. This study was aimed at understanding the molecular mechanisms by which TCAP-1 regulates these changes in the mouse hippocampus. Fluoresceinisothiocyanate (FITC)-labeled TCAP-1 binds to the pyramidal neurons of the CA2 and CA3, and dentate gyrus in the hippocampus of the mouse brain. Moreover, FITC-TCAP-1 co-localizes with ß-dystroglycan upon binding to the plasma membrane of cultured immortalized mouse E14 hippocampal cells. In culture, TCAP-1 stimulates ERK1/2-dependent phosphorylation of the cytoskeletal regulatory proteins, stathmin at serine-25 and filamin A at serine-2152. In addition, TCAP-1 induces actin polymerization, increases immunoreactivity of tubulin-based cytoskeletal elements and causes a corresponding increase in filopodia formation and mean filopodia length in cultured hippocampal cells. We postulate that the TCAP-1 region of teneurin-1 has a direct action on the cytoskeletal reorganization that precedes neurite and process development in hippocampal neurons. Our data provides novel evidence that functionally links the teneurin and dystroglycan systems and provides new insight into the molecular mechanisms by which TCAP-1 regulates cytoskeletal dynamics in hippocampal neurons. The TCAP-dystroglycan system may represent a novel mechanism associated with the regulation of hippocampal-function.