Monitoring Cochlear Health With Intracochlear Electrocochleography During Cochlear Implantation: Findings From an International Clinical Investigation.

OBJECTIVES: Electrocochleography (ECochG) is emerging as a tool for monitoring cochlear function during cochlear implant (CI) surgery. ECochG may be recorded directly from electrodes on the implant array intraoperatively. For low-frequency stimulation, its amplitude tends to rise or may plateau as the electrode is inserted. The aim of this study was to explore whether compromise of the ECochG signal, defined as a fall in its amplitude of 30% or more during insertion, whether transient or permanent, is associated with poorer postoperative acoustic hearing, and to examine how preoperative hearing levels may influence the ability to record ECochG. The specific hypotheses tested were threefold: (a) deterioration in the pure-tone average of low-frequency hearing at the first postoperative follow-up interval (follow-up visit 1 [FUV1], 4 to 6 weeks) will be associated with compromise of the cochlear microphonic (CM) amplitude during electrode insertion (primary hypothesis); (b) an association is observed at the second postoperative follow-up interval (FUV2, 3 months) (secondary hypothesis 1); and (c) the CM response will be recorded earlier during electrode array insertion when the preoperative high-frequency hearing is better (secondary hypothesis 2). DESIGN: International, multi-site prospective, observational, between groups design, targeting 41 adult participants in each of two groups, (compromised CM versus preserved CM). Adult CI candidates who were scheduled to receive a Cochlear Nucleus CI with a Slim Straight or a Slim Modiolar electrode array and had a preoperative audiometric low-frequency average thresholds of ≤80 dB HL at 500, 750, and 1000 Hz in the ear to be implanted, were recruited from eight international implant sites. Pure tone audiometry was measured preoperatively and at postoperative visits (FUV1 and follow-up visit 2 [FUV2]). ECochG was measured during and immediately after the implantation of the array. RESULTS: From a total of 78 enrolled individuals (80 ears), 77 participants (79 ears) underwent surgery. Due to protocol deviations, 18 ears (23%) were excluded. Of the 61 ears with ECochG responses, amplitudes were < 1 µV throughout implantation for 18 ears (23%) and deemed "unclear" for classification. EcochG responses >1 µV in 43 ears (55%) were stable throughout implantation for 8 ears and compromised in 35 ears. For the primary endpoint at FUV1, 7/41 ears (17%) with preserved CM had a median hearing loss of 12.6 dB versus 34/41 ears (83%) with compromised CM and a median hearing loss of 26.9 dB ( p < 0.014). In assessing the practicalities of measuring intraoperative ECochG, the presence of a measurable CM (>1 µV) during implantation was dependent on preoperative, low-frequency thresholds, particularly at the stimulus frequency (0.5 kHz). High-frequency, preoperative thresholds were also associated with a measurable CM > 1 µV during surgery. CONCLUSIONS: Our data shows that CM drops occurring during electrode insertion were correlated with significantly poorer hearing preservation postoperatively compared to CMs that remained stable throughout the electrode insertion. The practicality of measuring ECochG in a large cohort is discussed, regarding the suggested optimal preoperative low-frequency hearing levels ( < 80 dB HL) considered necessary to obtain a CM signal >1 µV.

Growth kinetics, improved plant growth and alleviation of water stress in tomato by water stress tolerant bacteria.

Plants are subject to a variety of abiotic stresses contributed to yield losses of up to 50%, posing a significant challenge to global food production. To cope with drought stress, of 205 bacterial cultures investigated for moisture stress tolerant potential, 16 cultures showed promising results in improving the majority of plant growth ameliorating activities under water stress and non-stress conditions. Growth kinetics and plant growth ameliorating activities declined significantly with the increase in water stress level. Most of the isolates tolerant to water stress were Streptomyces and Pseudomonas species. Of these, four strains with the best results were selected for growing tomato under water stress conditions. The imposition of water stress severely inhibited the growth of tomato plants. However, bacterial strains alleviated the stress and enhanced plant growth performance. Antioxidant activity showed a promising result of protection from reactive oxygen species produced in plants because of water stress. Plants treated with bioinoculants also exhibited a substantial decline in lipid peroxidation. Water stress significantly reduced the yield of tomato. However, bioinoculants treated plants demonstrated significantly higher yields than untreated plants. Nutrient uptake and fruit quality also improved in the treated plants. Experiments point to the scope of developing a microbial formulation to alleviate water stress in higher plants.

Endothelial activation is associated with intestinal epithelial injury, systemic inflammation and treatment regimen in children living with vertically acquired HIV-1 infection.

BACKGROUND: Premature development of cardiovascular disease in children living with HIV-1 (CLWH) may be associated with compromised gut barrier function, microbial translocation, immune activation, systemic inflammation and endothelial activation. Biomarkers of these pathways may provide insights into pathogenesis of atherosclerotic disease in CLWH. METHODS: This was a cross-sectional study of CLWH enrolled in the multicentre Early Pediatric Initiation-Canadian Child Cure Cohort (EPIC4 ) who were on antiretroviral therapy (ART) with undetectable viral load. Plasma biomarkers of intestinal epithelial injury [intestinal fatty acid binding protein-1 (IFABP)], systemic inflammation [tumour necrosis factor (TNF) and interleukin-6 (IL-6)] and endothelial activation [angiopoietin-2 (Ang2), soluble vascular endothelial growth factor-1 (sVEGFR1) and soluble endoglin (sEng)] were quantified by enzyme-linked immunosorbent assay. Correlation and factor analysis of biomarkers were used to examine associations between innate immune pathways. RESULTS: Among 90 CLWH, 16% of Ang2, 15% of sVEGFR1 and 23% of sEng levels were elevated relative to healthy historic controls. Pairwise rank correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61 and ρ = 0.65, P < 0.001 for all correlations). An endothelial activation index, derived by factor analysis of the three endothelial biomarkers, was correlated with TNF (ρ = 0.47, P < 0.001), IL-6 (ρ = 0.60, P < 0.001) and intestinal fatty acid binding protein-1 (ρ = 0.67, P < 0.001). Current or past treatment with ritonavir-boosted lopinavir (LPV/r) was associated with endothelial activation (odds ratio = 5.0, 95% CI: 1.7-17, P = 0.0020). CONCLUSIONS: Endothelial activation is prevalent in CLWH despite viral suppression with combination ART and is associated with intestinal epithelial injury, systemic inflammation and treatment with LPV/r.

Energy and carbon budgeting of traditional land use change with groundnut based cropping system for environmental quality, resilient soil health and farmers income in eastern Indian Himalayas.

Energy intensive traditional cereals based monoculture often lead to high greenhouse gas emissions and degradation of land and environmental quality. Present study aimed at evaluating the energy and carbon budget of diversified groundnut (Arachis hypogea L) based cropping system with over existing traditional practice towards the development of a sustainable production technology through restoration of soil and environmental quality and enhancement of farming resiliency by stabilizing farmers' income. The trials comprised of three introduced groundnut based systems viz. groundnut- pea (Pisum sativum), groundnut-lentil (Lens esculenta) and groundnut-toria (Brasssica campestris var. Toria) replacing three existing systems viz. maize (Zea mays L) - fallow, maize - toria, and rice (Oryza sativa L)-fallow systems. Four years study revealed that adoption of groundnut based systems reduced non-renewable energy input use (fertilizers, chemical, machinery and fossil fuels) by 25.5%, consequently that reduced the cost of production. Repeated analysis of variance measurement also affirmed that groundnut based systems (groundnut-pea>groundnut-lentil> groundnut-toria) increased the energy use efficiency, energy productivity, carbon use efficiency, net returns and decreased the specific energy and energy intensiveness. Groundnut based systems increased the mean system productivity and water productivity in terms of groundnut equivalent yield by 3.7 and 3.1 folds over existing practice. The savings of fossil fuel reduced greenhouse gas emissions owing to reduced use of farm machinery and synthetic fertilizers. Groundnut based systems significantly (p < 0.05) enhanced the soil carbon concentration (8.7-18.1%) and enzymatic activities (27.1-51.8%) over existing practice. Consequently, estimated soil quality index values were 35.9-77.3% higher under groundnut based systems than existing practice. Thus, the study indicated the resilient nature of groundnut based systems as an environmentally safe and sustainable production technology for enhancing resource use efficiency, reduce carbon emission, energy intensiveness and cost of production in the Eastern Himalaya region of India and similar ecosystems.

Isolation and characterization of endophytic bacteria from tomato foliage and their in vitro efficacy against root-knot nematodes.

Fifteen endophytic bacteria were isolated from leaves and stems of Solanum lycopersicum and Solanum pimpinellifolium collected from different locations of the Jorhat district of Assam and characterized by morphological, cultural, biochemical and molecular approaches. An in vitro study was carried out to evaluate their potentiality as biological control agents against second stage juvenile of the root-knot nematode, Meloidogyne incognita race2. Thirty second stage juveniles (J2) of M. incognita race 2 were exposed to cell free culture filtrates of all the 15 bacterial endophytes in a sterile cavity block at a concentration of S(100%), S/2(50%), S/4(25%), S/6(17%) and S/10(10%) for a duration of 6, 12, 24, and 48 hr. The results revealed that all the isolates had the potentiality to significantly increase the mortality of the second stage juveniles (J2). The percent mortality was directly proportional to the duration of exposure time and the concentration of the culture filtrate. The isolate BETL2 showed the best result with 81.47% mortality of juveniles followed by isolates BETL4 (81.43%), BETLI (79.07%), BETS2 (78.87%), and BETL6 (78.17%). The 16S rRNA sequence amplification results indicated that these isolates were Bacillus marisflavi (BETL2), Bacillus altitudinis (BETL4), Microbacterium arborescens (BETL1), Exiguobacterium indicum (BETS2), and Bacillus marisflavi (BETL6). The four most efficient isolates were structurally analyzed using a scanning electron microscope and this revealed that the length and breadth of isolates-BETLI, BETL2, BETL4, and BETS2 were 701.70 nm × 348.30 nm, 954.10 nm × 303.10 nm, 984.10 nm × 332.90 nm and 1422.00 nm × 742.00 nm, respectively. The result of the present study indicated that the above four novel strains of endophytic bacterial isolates enhance the mortality of J2 of M. incognita race2 and has the potentiality as biological control agents against M. incognita.

Interlaboratory Comparison of Six Real-Time PCR Assays for Detection of Bovine Leukemia Virus Proviral DNA.

Quantitative real-time PCR (qPCR) is increasingly being used for the detection of bovine leukemia virus (BLV) proviral DNA. Nevertheless, quality control for the validation and standardization of such tests is currently lacking. Therefore, the present study was initiated by three Office International des Epizooties (OIE) reference laboratories and three collaborating laboratories to measure the interlaboratory variability of six already developed and available BLV qPCR assays. For that purpose, an international panel of 58 DNA samples reflecting the dynamic range of the majority of the assays was distributed to six testing centers. Based on qualitative results, the overall agreement among all six laboratories was moderate. However, significant variability in the measurement of the BLV proviral DNA copy number was observed among different laboratories. Quantitative PCR assays, even when performed by experienced staff, can yield large variability in BLV proviral DNA copy numbers without harmonization. Further standardization of different factors (i.e., utilization of unified protocols and unique calibrators) should increase interlaboratory agreement.

The effect of microbial activity on soil water diffusivity.

In this study, we explored the effects of microbial activity on the evaporation of water from cores of a sandy soil under laboratory conditions. We applied treatments to stimulate microbial activity by adding different amounts of synthetic analogue root exudates. For comparison, we used soil samples without synthetic root exudates as control and samples treated with mercuric chloride to suppress microbial activity. Our results suggest that increasing microbial activity reduces the rate of evaporation from soil. Estimated diffusivities in soil with the largest amounts of added root exudates were one third of those estimated in samples where microbial activity was suppressed by adding mercuric chloride. We discuss the effect of our results with respect to water uptake by roots. HIGHLIGHTS: We explored effects of microbial activity on the evaporation of water from cores of a sandy soil.We found the effect of microbial activity on water release characteristic was small.Increasing microbial activity reduced evaporation from soil, while microbial suppression increased it.Effect of microbial activity on root water uptake was estimated to be equivalent to a change in soil structure.

Refractive index sensing in the visible/NIR spectrum using silicon nanopillar arrays.

Si nanopillar (NP) arrays are investigated as refractive index sensors in the visible/NIR wavelength range, suitable for Si photodetector responsivity. The NP arrays are fabricated by nanoimprint lithography and dry etching, and coated with thin dielectric layers. The reflectivity peaks obtained by finite-difference time-domain (FDTD) simulations show a linear shift with coating layer thickness. At 730 nm wavelength, sensitivities of ~0.3 and ~0.9 nm/nm of SiO2 and Si3N4, respectively, are obtained; and the optical thicknesses of the deposited surface coatings are determined by comparing the experimental and simulated data. The results show that NP arrays can be used for sensing surface bio-layers. The proposed method could be useful to determine the optical thickness of surface coatings, conformal and non-conformal, in NP-based optical devices.

ZnO nanowire-enabled light funneling effect for antireflection and light convergence applications.

We present a new light trapping technique to reduce reflection loss, as well as for light, focusing at submicron scales for solar cell and image sensing applications. We have fabricated hexagonal arrays of ZnO funnel-like structures on Si substrate by the patterned growth of ZnO nanowires in a hydrothermal growth process. The funnels are optimized so that the effective refractive index along the vertical direction decreases gradually from the Si surface to the top of funnel to reduce Fresnel reflection at a device-air interface. Finite difference time domain simulation is used for optimization of the minimum reflectivity and to analyze optical properties such as angle dependency, polarization dependency, and funneling effect. The structures function similar to a GRIN lens in light trapping and convergence. An optimized structure reduces the average reflectivity close to 3% in the wavelength range of 300-1200 nm with the possibility of confining incident light to a few hundreds of nanometers.

Response of water deficit regime and soil amelioration on evapotranspiration loss and water use efficiency of maize (Zea mays l.) in subtropical northeastern Himalayas.

Rainfed maize production in the hilly ecosystem of Northeastern Himalayas often suffers from moisture and soil acidity induced abiotic stresses. The present study measured evapotranspiration loss (ETc) of maize crop under controlled condition (pot experiment) of water deficit (W25-25 % and W50-50 % of field capacity soil moistures) and well watered (W100 = 100 % of field capacity (FC)) regimes in strong acid soils (pH = 4.3) of the Northeastern Himalayan Region of India. The response of soil ameliorants (lime) and phosphorus (P) nutrition under differential water regimes on ETc losses and water use efficiency was also studied. The measured seasonal ETc loss varied from 124.3 to 270.9 mm across treatment combinations. Imposition of water deficit stress resulted in significant (p < 0.05) reduction (by 33-50 %) of seasonal ETc losses but was at the cost of delay in tasseling to silking, 47-65 % reduction in dry matter accumulation (DMA), 12-22 days shortening of grain formation period, and complete kernel abortion. Liming @ 4 t ha-1 significantly (p < 0.05) increased ETc losses and DMA across water regimes but the magnitude of increase was higher in severely water deficit (W25) regime. Unlike lime, P nutrition improved DMA only in well-watered regimes (W100) while seasonal ETc loss was unaffected. Vegetative stage (tillering to tasseling) contributed the maximum ETc losses while weekly crop ETc loss was estimated highest during 11th-14th week after sowing (coincided with blistering stage) and then declined. Water use efficiency estimated from dry matter produced per unit ETc losses and irrigation water used varied from 4.33 to 9.43 g dry matter kg-1 water and 4.21 to 8.56 g dry matter kg-1, respectively. Among the input factors (water, P, and lime), water regime most strongly influenced the ETc loss, growth duration, grain formation, and water use efficiency of maize.

Surface second harmonic generation from silicon pillar arrays with strong geometrical dependence.

We present experimental demonstration and analysis of enhanced surface second harmonic generation (SHG) from hexagonal arrays of silicon pillars. Three sets of Si pillar samples with truncated cone-shaped pillar arrays having periods of 500, 1000, and 2000 nm, and corresponding average diameters of 200, 585 and 1550 nm, respectively, are fabricated by colloidal lithography and plasma dry etching. We have observed strong dependence of SHG intensity on the pillar geometry. Pillar arrays with a 1000 nm period and a 585 nm average diameter give more than a one order of magnitude higher SHG signal compared to the other two samples. We theoretically verified the dependence of SHG intensity on pillar geometry by finite difference time domain simulations in terms of the surface normal E-field component. The enhanced surface SHG light can be useful for nonlinear silicon photonics, surface/interface characterization, and optical biosensing.

Monsoon variability, crop water requirement, and crop planning for kharif rice in Sagar Island, India.

In the Sagar Island of Bay of Bengal, rainfed lowland rice is the major crop, grown solely depending on erratic distribution of southwest monsoon (SM) rainfall. Lack of information on SM rainfall variability and absence of crop scheduling accordingly results in frequent occurrence of intermittent water stress and occasional crop failure. In the present study, we analyzed long period (1982-2010) SM rainfall behavior (onset, withdrawal, rainfall and wetness indices, dry and wet spells), crop water requirement (CWR, by Food and Agriculture Organization (FAO) 56), and probability of weekly rainfall occurrence (by two-parameter gamma distribution) to assess the variability and impact on water availability, CWR, and rice productivity. Finally, crop planning was suggested to overcome monsoon uncertainties on water availability and rice productivity. Study revealed that the normal onset and withdrawal weeks for SM rainfall were 22nd ± 1 and 43rd ± 2 meteorological weeks (MW), respectively. However, effective monsoon rainfall started at 24th MW (rainfall 92.7 mm, p > 56.7 % for 50 mm rainfall) and was terminated by the end of 40th MW (rainfall 90.7 mm, p < 59.6 % for 50 mm rainfall). During crop growth periods (seed to seed, 21st to 45th MW), the island received an average weekly rainfall of 65.1 ± 25.9 mm, while the corresponding weekly CWR was 47.8 ± 5.4 mm. Despite net water surplus of 353.9 mm during crop growth periods, there was a deficit of 159.5 mm water during MW of 18-23 (seedling raising) and MW of 41-45 (flowering to maturity stages). Water stress was observed in early lag vegetative stage of crop growth (32nd MW). The total dry spell frequency during panicle initiation and heading stage was computed as 40 of which 6 dry spells were >7 days in duration and reflected a significant (p < 0.05) increasing trend (at 0.22 days year(-1)) over the years (1982-2010). The present study highlights the adaptive capacity of crop planning including abiotic stress-tolerant cultivars to monsoon rainfall variability for sustaining rainfed rice production vis-à-vis food and livelihood security in vulnerable islands of coastal ecosystem.

The ecology and age structure of a highly pathogenic avian influenza virus outbreak in wild mute swans.

The first UK epizootic of highly pathogenic (HP) H5N1 influenza in wild birds occurred in 2008, in a population of mute swans that had been the subject of ornithological study for decades. Here we use an innovative combination of ornithological, phylogenetic and immunological approaches to investigate the ecology and age structure of HP H5N1 in nature. We screened samples from swans and waterbirds using PCR and sequenced HP H5N1-positive samples. The outbreak's origin was investigated by linking bird count data with a molecular clock analysis of sampled virus sequences. We used ringing records to reconstruct the age-structure of outbreak mortality, and we estimated the age distribution of prior exposure to avian influenza. Outbreak mortality was low and all HP H5N1-positive mute swans in the affected population were <3 years old. Only the youngest age classes contained an appreciable number of individuals with no detectable antibody responses to viral nucleoprotein. Phylogenetic analysis indicated that the outbreak strain circulated locally for ~1 month before detection and arrived when the immigration rate of migrant waterbirds was highest. Our data are consistent with the hypothesis that HP H5N1 epizootics in wild swans exhibit limited mortality due to immune protection arising from previous exposure. Our study population may represent a valuable resource for investigating the natural ecology and epidemiology of avian influenza.

Reducing mortality in mucormycosis of the head and neck in diabetic patients: A CARE case series.

INTRODUCTION: Rhinocerebral mucormycosis is extremely fatal, with mortality rates ranging from 85-93% despite the best treatment in immunocompromised patients. We emphasize the importance of early diagnosis, repeated debridement, and aggressive antifungal treatment to reduce mortality. CASE SUMMARY: We report six cases (five male and one female), with a mean age of 51 years who were diagnosed to have mucormycosis from 2017 to 2019. All patients were diabetic. Intracranial involvement and orbital involvement were found in four cases. Facial nerve palsy was seen in two cases, one without any apparent otological involvement. Aggressive serial debridement and amphotericin B was started. Posaconazole was added subsequently to the treatment in two cases. One patient succumbed to the disease five months after discharge. The other five patients are on regular follow-up for a mean duration of 14 months at the end of which two had residual disease which was under control. DISCUSSION: Repeated surgical debridement with an early aggressive and combination antifungal therapy can result in good outcomes even in advanced mucormycosis. Concurrent management of the underlying pathology, monitoring of liver and kidney functions, and therapeutic drug monitoring are useful to ensure smooth and effective treatment.

Occurrence & antibiogram of Salmonella Typhi & S. Paratyphi A isolated from Rourkela, Orissa.

BACKGROUND & OBJECTIVES: Almost round-the-year occurrence of Salmonella Typhi and Salmonella Paratyphi A has been noticed in Rourkela since last 13 and five years respectively. The incidence of infection along with the antibiogram of these two serotypes in this area were carried out. METHODS: The study was carried out at Ispat General Hospital, Rourkela, India, between January 2005 and December 2008 with 5340 blood samples collected from patients with suspected enteric fever and pyrexia of unknown origin. Isolation, identification and antibiogram of the causative organisms were performed according to standard bacteriological procedures. RESULTS: A total of 298 Salmonella isolates showed an overall per cent positivity of 5.58. Multidrug resistance was found in 11.96 per cent and 15.62 per cent isolates of S. Typhi and S. Paratyphi A respectively. Less than 2 per cent isolates of Salmonella showed resistance to ciprofloxacin. A resistance of 3.0 to 6.25 per cent against third generation cephalosporins was observed among the salmonella isolates. INTERPRETATION & CONCLUSION: A round-the-year occurrence of Salmonella spp. in Rourkela might have been due to the presence of a considerable number of carriers in the locality, poor sanitation in nearby slum areas, and inadequate and contaminated community water supply at times. Higher degree of susceptibility among S. Typhi isolates against various antibiotics was encouraging, but increasing trend of resistance observed among S. Paratyphi A isolates was a matter of concern.

Mucin-derived O-glycans supplemented to diet mitigate diverse microbiota perturbations.

Microbiota-accessible carbohydrates (MACs) are powerful modulators of microbiota composition and function. These substrates are often derived from diet, such as complex polysaccharides from plants or human milk oligosaccharides (HMOs) during breastfeeding. Host-derived mucus glycans on gut-secreted mucin proteins serve as a continuous endogenous source of MACs for resident microbes; here we investigate the potential role of purified, orally administered mucus glycans in maintaining a healthy microbial community. In this study, we liberated and purified O-linked glycans from porcine gastric mucin and assessed their efficacy in shaping the recovery of a perturbed microbiota in a mouse model. We found that porcine mucin glycans (PMGs) and HMOs enrich for taxonomically similar resident microbes. We demonstrate that PMGs aid recovery of the microbiota after antibiotic treatment, suppress Clostridium difficile abundance, delay the onset of diet-induced obesity, and increase the relative abundance of resident Akkermansia muciniphila. In silico analysis revealed that genes associated with mucus utilization are abundant and diverse in prevalent gut commensals and rare in enteric pathogens, consistent with these glycan-degrading capabilities being selected for during host development and throughout the evolution of the host-microbe relationship. Importantly, we identify mucus glycans as a novel class of prebiotic compounds that can be used to mitigate perturbations to the microbiota and provide benefits to host physiology.

Variability in symbiotic effectiveness of native Rhizobia in acid stress.

In vitro experiments had been conducted to assess the effect of pH on different native isolates of Rhizobium from the lower Brahmaputra valley region of Assam, India. The growth rate of all the Rhizobium isolates were compared growing at three different pH levels viz. 4.5, 5.5 and 6.5. All the slow-growing Rhizobium isolates (AR1, BR5, BR8, BR12, GR13, AR10, BR13, GM16, GR21) were showed better growth at all the pH levels, whereas three fast-growing Rhizobium isolates (PR7, PR12 and PR16) failed to grow at pH 4.5 and 5.5 and could show growth only at pH 6.5. Experiments were also conducted in vitro to determine the symbiotic effectiveness of all the Rhizobium isolates with test legume, green gram (Phaseolus aureus Roxb.) at three different pH levels for 42 days and significant differences were observed on nodulation, nodule dry weight and nitrogenase activity. The acid-tolerant isolates could be used as bioinoculant for enhancement of growth of leguminous plants in the acid soils.

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition.

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies.

Nitrilase-catalysed conversion of acrylonitrile by free and immobilized cells of Streptomyces sp.

The biotransformation of acrylonitrile was investigated using thermophilic nitrilase produced from a new isolate Streptomyces sp. MTCC 7546 in both the free and immobilized state. Under optimal conditions,the enzyme converts nitriles to acids without the formation of amides.The whole cells of the isolate were immobilized in agar-agar and the beads so formed were evaluated for 25 cycles at 50 degrees C. The enzyme showed a little loss of activity during reuse. Seventy-one per cent of 0.5 M acrylonitrile was converted to acid at 6 h of incubation at a very low density of immobilized cells, while 100% conversion was observed at 3 h by free cells.

Incursion of Schmallenberg virus into Great Britain in 2011 and emergence of variant sequences in 2016.

Schmallenberg virus (SBV) is a vector-borne orthobunyavirus in the family Bunyaviridae, first identified in Germany before rapidly spreading throughout Europe. To investigate the events surrounding the incursion of this virus into Great Britain (GB) and its subsequent spread, archived sheep serum samples from an unrelated field survey in 2011 were analysed for the presence of SBV specific antibodies, to determine the earliest date of seroconversion. This serological study, along with analysis of the spatial spread of the sources of samples submitted for SBV analysis after January 2012, suggests that SBV entered GB on more than one occasion and in more than one location. Phylogenetic analysis of SBV sequences from 2012 ovine samples, from a variety of counties and dates, demonstrated a non-linear evolution of the virus, i.e. there was no distinct clustering between host species, geographical locations or during the outbreak. This also supports the notion of multiple viruses entering GB, rather than a single virus incursion. Premature termination signals were present in several non-structural putative protein sequences. One SBV sequence exhibited large deletions in the M segment of the genome. After the first outbreak in 2011-2012, interest in SBV in GB waned and continuous surveillance was not upheld. The re-emergence of SBV in 2016 has raised renewed concern and ended speculation that SBV might have been eradicated permanently from GB. When SBV sequences from 2012 were compared with those from the re-emergence in 2016-2017, a second distinct clade of SBV was identified that separates recent strains from those observed during the first outbreak.