ADVERSE DRUG REACTION MONITORING AMONG HYPERTENSIVE PATIENTS OF TERTIARY CARE CENTER OF NORTH INDIA RELATED TO ANTIHYPERTENSIVE DRUGS

Objective: The objective of the study was to monitor the adverse drug reactions (A.D.Rs.) associated with antihypertensive drugs. Methods: All patients coming to the department with blood pressure systolic above 120 mmHg and diastolic above 90 mmHg and prescribed hypertensives will be screened for the study. Results and Discussion: A total of 136 patients were observed during the study. Out of 136 patients, 23 (17%) A.D.Rs. were recorded. A study conducted by Ramesh et al. in the Indian capital reports that 22.3% of the patients experienced A.D.Rs. Conclusion: Furthermore, any appearance of A.D.Rs. due to side effects of the drugs or due to bad control and patients non-compliance, it was treated mainly by decreasing the doses of the drugs, switching them to another active substance from the same pharmacological group, or by adding more active substances from different pharmacological groups in lower dosages to achieve the B.P goals

The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells

Different from canonical ubiquitin-like proteins, Hub 1 does not form covalent conjugates with substrates but binds proteins non- covalently. In Saccharomyces cerevisiae , Hub 1 associates with spliceosomes and mediates alternative splicing of SRC 1 , without affecting pre-mRNA splicing generally. Human Hub 1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub 1 binds to the spliceosomal protein Snu 66 as in yeast; however, unlike its S. cerevisiae homolog, human Hub 1 is essential for viability. Prolonged in vivo depletion of human Hub 1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe, and consequently cell death by apoptosis. Early consequences of Hub 1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub 1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing

Sero-prevalance of Cryptococcal Antigenemia in HIV Positive Individual having CD4 Counts

Cryptococcus neoformans is one of the foremost common opportunistic infectious agents in people living with Acquired Immuno Deficiency Syndrome (AIDS). It has been reported to cause about 1 million cases of cryptococcal meningitis per year among HIV/AIDS and 600,000 deaths annually. This study was done to find the prevalence of Cryptococcal antigenemia among HIV positive individuals having CD4counts <100 cells/mm3. A cross-sectional study was conducted in the HIV Reference unit, National public health laboratory from July to December 2015. The study comprised of 99 HIV positive individuals having CD4counts <100 cells/mm3. CD4 T cell count was performed by flow cytometry (BD Biosciences, San Jose, CA, USA) and Cryptococcal antigen test by Latex agglutination assay. The overall prevalence of cryptococcal antigenemia was found to be 18.2%. Of the total ninety-nine subjects enrolled in the study, 72 (72.8%) were males and 27 (27.2%) were females. The mean age of the patients was 38 years ranging from 13 to 69 years. Higher percentage of female (22.2%) showed Cryptococcal infection in our study as compared to male (16.7%). The study concludes higher prevalence of Cryptococcal antigenemia among HIV infected individuals and recommends Cryptococcal antigen screening to be made mandatory in HIV positive patients having CD4 T cells count below 100/μl

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Tomato heat stress transcription factor HsfA1 as master regulator of thermotolerance

The heat stress (hs) response is universal to all organisms. As the cell senses increase in temperature, heat stress transcription factors (Hsfs) are activated to upregulate the expression of a number of genes encoding heat stress proteins (Hsp) which act as molecular chaperones to protect cells against heat damages. In higher plants, the phenomenon seems to be unusually complex both at the level of Hsfs and Hsps (e.g., 21 Hsf encoding genes in Arabidopsis and at least 17 in tomato). Upon prolonged hs, another characteristic property of plant cells is the assembly of large cytosolic aggregates called heat stress granules (HSG), which are composed of Hsps, HsfA2, RNA and RNA-binding proteins. The present work was aimed to understand plant hs response using tomato as a model system. To study the function of tomato Hsfs in their native system, we generated transgenic tomato lines altered in expression of HsfA1, HsfA2, and HsfB1. Tomato plants with 10-fold overexpression of HsfA1 (OE plants) were characterised by integration of a single HsfA1 expression cassette, whereas the plants harbouring a tandem inverted repeat (IR) of the cassette showed cosuppression of HsfA1 (CS plants). The lack of HsfA1 expression in CS plants results from posttranscriptional gene silencing connected with the formation of small interfering RNA (siRNA). Under normal growth conditions, major developmental features were similar for wild-type (WT), OE and CS plants. However, in contrast to the former two, CS plants and fruits were extremely sensitive to elevated temperature because hs-induced synthesis of major chaperones and Hsfs was strongly reduced or lacking. Despite the complexity of the plant Hsf family, the function of tomato HsfA1 is unique as master regulator of induced thermotolerance. On the other hand, maintenance of essential chaperones in CS plants during seed development suggests involvement of other Hsfs and/or transcription factor(s). HsfB1 and HsfA2 transgenic tomato plants, unaffected in thermotolerance, further supported the function of HsfA1 as the major factor regulating hs-inducible genes. Hs87 independent phenotypes of plants with altered expression of HsfB1 indicates developmental role of this Hsf. Using transient reporter assays with mesophyll protoplasts from WT tomato, we demonstrated that plasmids encoding Hsfs A1, A2 and A3 were well expressed which could function as activators for reporter gene expression. However, in protoplasts derived from CS plants, plasmids encoding HsfA2 and HsfA3 were normally expressed but even higher amounts of HsfA1 expression plasmids were completely silenced. Therefore, silencing of HsfA1 in CS plants was also reproduced in its mesophyll protoplasts. Lacking thermotolerance in CS protoplasts could be restored after transformation with expression plasmids encoding functionally equivalent HsfA2 or HsfA3 resulting in (i) expression of chaperones, (ii) survival of the cells at otherwise lethal temperature, (iii) thermoprotection of firefly luciferase, and (iv) assembly of heat stress granules (HSGs). The strong silencing caused by an IR in CS plants opened the possibility of a broad use of RNAi for gene knock-down also in the transient system of mesophyll protoplasts. Using this technology, we attempted to dissect essential components of thermotolerance and HSG assembly. We demonstrated the previously reported function of chaperones such as Hsp70 and Hsp101, and could discriminate the in vivo chaperone functions of different isoforms of Hsp20 and Hsp70 proteins. Hsp17-CI, Hsp70 (hs-inducible isoforms), and Hsp101 are absolutely essential chaperones for thermotolerance in plants. Furthermore, the results also show that despite Hsp17-CI and -CII being major components of HSG complexes, they are dispensable for assembly of these complexes. Based on these results, it is proposed that in the transient protoplast system an approach with gene-specific IRs can be used to discriminate functions of closely related isoforms among protein-families and to dissect complex protein networks.Aufgrund der sessilen Lebensform sind Pflanzen in besonderer Weise den ständig wechselnden Umweltbedingungen ausgesetzt. Das erfordert ein ungewöhnliches Mass an Anpassungsfähigkeit, damit Überleben und Entwicklungsfähigkeit mit Blüten-, Frucht- und Samenbildung auch unter diesen Umständen gewährleistet sind. Im Vergleich mit anderen Organismen, ist ein auffälliges Merkmal von Pflanzen die Komplexität der Stressantwortsysteme. Das gilt in besonderer Weise für die Vielfalt von Chaperonen und regulatorischen Proteinen (Hitzestresstranscriptionsfaktoren, Hsf), die die Antwort auf erhöhte Temperaturen (Hitzestressantwort) kennzeichnt. Die jüngsten Erfolge der Genomanalyse bei Arabidopsis und Reis sowie die Verfügbarkeit von umfangreichen internationalen Datenbanken mit sogenannten expressed sequence tags (ESTs) haben ergeben, dass insgesamt mehr als 20 Hsfs, die in drei unterschiedlichen Strukturklassen eingeteilt werden können, in irgend einer Weise an der Regulation der Hitzestressantwort bei Pflanzen beteiligt sind. Ziel der Arbeit war die Untersuchung von Tomatenmutanten mit veränderten Expressionsmustern von Chaperonen und Hitzestresstranscriptionsfaktoren, um Einblicke in die funktionelle Diversifizierung der beteiligten Komponenten zu erhalten. Ausgangspunkt waren Tomatenpflanzen mit Insertionen von Sense- und Antisense- Kassetten für HsfA1, HsfA2 und HsfB1. Entscheidend für die Entwicklung der experimentellen Arbeiten war zunächst eine einzige primär transgene T0 Pflanze mit mehreren Insertionen der Sense Kassette von HsfA1, die im Verlauf unserer weiteren Züchtungsarbeiten in mehrere Linien aufspaltete. Eine Linie mit einer einzigen Transgenkassette hatte eine etwa 10-fach erhöhte Expression von HsfA1 (overexpression line OE). Zwei weitere Linien waren gekennzeichnet durch eine Tandem Integration von 2 Transgenkassetten mit invertierter Anordnung (IR). Dieses führt zu Cosuppressionseffekten (CS2 und CS3 Linien), d.h. nicht nur die Expression des Transgens sondern auch die des Endogens von HsfA1 wird unterbunden. Die Zahl der eingebauten Kassetten im Genom und ihre Anordnung wurden mit Hilfe von Southern Blots und PCR Analysen aufgeklärt. Nach der Aufspaltung und Selektion der homozygoten Linien waren die Erbeigenschaften und Phänotypen der drei erhaltenen Linien (OE, CS2, CS3) über viele Generationen stabil. Der molekulare Mechanismus der Cosuppression konnte in unserem Fall eindeutig auf die Bildung von sogenannter „interference RNA“ (RNAi) zurückgeführt werden. Die Anordnung der beiden Transgenkassetten als inverted repeat (IR) führt zur Synthese von mRNA Molekülen mit Informationen vom Sense- und Antisensestrang des HsfA1 Gens. Die daraus resultierende Bildung von RNA-Haarnadelstrukturen wird in den Zellen von einem Endonukleasekomplex als abartig erkannt (DICER Komplex) und in kurze Doppelstrang RNA Fragmente von etwa 21 Nukleotiden zerlegt. Diese dienen als Führungs-RNA (guide RNA) für einen weiteren RNAse Komplex (RISC Komplex), der die selektive Zerstörung der HsfA1 mRNA bewirkt. Der ganze Prozess wird als posttranscriptional gene silencing (PTGS) bezeichnet. Durch Auftrennung der Fraktion kleiner RNAs aus Tomatengewebe und entsprechende Hybridisierung konnten wir die Existenz dieser RNAi Moleküle in den CS Pflanzen nicht aber in WT und OE Pflanzen nachweisen. Überraschend waren die tiefgreifenden Auswirkungen der veränderten Expression von HsfA1 in den transgenen Pflanzen. Im Vergleich zu Wildtyp-Pflanzen war in den HsfA1 Überexpressionslinien (OE) die Expression der Hitzestress-induzierten Gene stark gesteigert und fand in einigen Geweben auch unabhängig von einer Stressinduktion statt. Im Gegensatz dazu fehlten praktisch alle Hitzestress-induzierten Proteine in den Cosuppresionsslinien (CS). Das war deshalb überraschend, weil wir angenommen hatten, dass der Expressions Knock-out eines der 20 Hsfs durch die Aktivität verwandter Hsfs ausgeglichen werden könnte. Das ist offensichtlich nicht der Fall. HsfA1 ist der Master-Regulator der Hitzestressantwort in Tomate. Bei Versuchen mit Tomatenpflanzen im Gewächshaus unter den erhöhten Stressbedingungen des Sommers 2003 oder aber auch in Klimakammern mit erhöhten Temperaturen konnte man die drastischen Folgen des Ausfalls von HsfA1 direkt beobachten. Die Pflanzen im vegetativen Zustand waren gegenüber dem Wildtyp extrem Temperatur-empfindlich, und die Fruchtreifung kam vollständig zum Erliegen. Auf der anderen Seite haben wir keinerlei Unterschiede in Wachstum und Entwicklung (Blütenansatz, Fruchtreifung, Samenkeimung etc.) zwischen den drei Linien beobachtet, wenn sie bei 25°C gehalten wurden. Auch die entwicklungs-spezifische Expression von Chaperonen bei der Samenreifung war unverändert. Offensichtlich spielt HsfA1 dabei keine nennenswerte Rolle. Es wird sogar während der Samenreifung selektiv abgebaut und wird erst in der frühesten Phase der Samenkeimung wieder nachweisbar. Dieser interessante Vorgang liess sich sehr klar am Beispiel der OE Pflanzen belegen. Zur experimentellen Verifizierung der an ganzen Pflanzen beobachteten Effekte wurde ein transientes Genexpressionssystem mit Mesophyllprotoplasten aus steril angezogenen Tomatenpflanzen der drei Linien (WT, OE, CS3) neu etabliert. Entsprechend unseren langjährigen Erfahrungen mit Tabakmesophyllprotoplasten, lassen sich auch die Tomatenprotoplasten relativ einfach in Gegenwart von Polyethylenglykol transformieren und zu Reporterassays und in situ Chaperonassays nutzen. Die Ergebnisse mit Protoplasten aus den CS3 Pflanzen sind besonders aufschlussreich. Die durch den Ausfall von HsfA1 fehlende Kapazität zur Expression von Hitzestressinduzierten Genen und damit zur Ausbildung von Themotoleranz kann durch Tranformation mit verschiedenen, nahe verwandten Hsfs repariert werden (HsfA2, HsfA3, HsfA4b). Diese durch entsprechende Expressionsplasmide eingebrachten Hsfs sind also funktionell äquivalent zu HsfA1 und können ihn sogar in der Stärke der Genexpression übertreffen, aber sie stehen in den ganzen Pflanzen nicht zur Verfügung. Warum das so ist, konnten wir nur für HsfA2 eindeutig klären. Dieser ist ein strikt Hitzestress-induziertes Protein und daher in seiner Expression ebenfalls von HsfA1 als Masterregulator abhängig. Im Rahmen meiner Untersuchungen habe ich auch andere transgene Tomaten-Linien einbezogen, in denen die Expression von HsfA2 und HsfB1 durch Antisense Konstrukte ausgeschaltet waren, und eine Linie mit Überexpression von HsfB1. Unabhängig von den Testbedingungen (Kontrolle oder Hitzestress) waren die Phänotypen bei weitem nicht so deutlich wie bei den Linien mit geänderter Expression von HsfA1. Dennoch sind zwei Beobachtungen sehr aufschlussreich für die Beurteilung der besonderen Rolle von HsfB1 für die Entwicklung der Pflanzen. Die konstitutive Expression von HsfB1 in den HsfB1 Sense Pflanzen führt zu einem gedrungenen Wachstum und vorzeitigem Fruchtansatz, während das Fehlen von HsfB1 in den Antisensepflanzen zwar keinen sichtbaren Effekt auf die Themotoleranz hat, aber zu einem vorzeitigen Altern und Absterben der Pflanzen führt. Die erfolgreichen Arbeiten zur Charakterisierung der HsfA1 CS Linien und der Wiederherstellung der Thermotoleranz in entsprechenden Mesophyllprotoplasten hat einen neuen para-genetischen Zugang zur Analyse der komplexen Proteinnetzwerke ermöglicht, die an dem Phänomen der Thermotoleranz beteiligt sind. Dafür wurden im Grundansatz Mesophyllprotoplasten mit Plasmiden transformiert, die für HsfA2 und/oder HsfA3 kodierten und ein Plasmid, das für Luciferase aus Photinus pyralis (Glühwürmchen) als thermosensitivem, leicht nachweisbarem Reporterprotein kodiert. Wir konnten in diesem Messansatz in den Protoplasten den Schutz der Luciferase gegen thermische Denaturierung bei 41°C (30 Minuten) und die nachfolgende Renaturierung für 120 Minuten bei 25°C als Wirkung des zelleigenen Chaperonsystems analysieren. Mit Hilfe von genspezifischen IR-Konstrukten haben wir aber auch die Bildung der entsprechenden RNAi in dem transienten Reporterassay benutzt, um die Bildung einzelner Komponenten des Chaperonsystems zu verhindern und damit ihre Rolle für Proteinfaltung und Proteintopogenese in einem transienten Expressionssystems zu untersuchen

Multilayer Thermal Barrier Coating prepared by EB-PVD process and its structure property correlation

The present work discusses our findings on development of nanostructured Yttria Stabilized Zirconia (YSZ), Lanthanum Zirconate (LZ) coatings, bond coat (NiCrAl) and their Multilayer coatings by electron beam evaporation for potential thermal barrier applications. The YSZ and LZ coatings were found to have cubic FCC phase and amorphous phase respectively. The grain sizes were found to be less than 50 nm in all the layers as observed by AFM and FEG SEM. A detailed cross sectional microstructure and compo-sitional analysis revealed the presence of different layer near to stoichiometry. X-ray diffraction confirmed the formation of desired phases in different layers. The cry-stallite sizes were found to be less than 50 nm, as esti-mated by X-ray diffraction peaks by Debye Sherrer equat-ion. Nanoindentation studies were carried out for study-ing the mechanical behavior of the single and multilayered coatings.Thermal diffusivity was assessed for YSZ coatings

Efficacy and Economics of Plant Extract and Chemicals Insecticide, against Mustard Aphid, Lipaphis erysimi (Kalt)

The field experiment conducted at the Student Instructional Farm (SIF), Chandra Shekhar Azad University of Agriculture & Technology Kanpur during the Rabi season of 2021-2022. The experiment focused on the Indian mustard variety Varuna and included eight treatments, including a control plot. Among the treatments, it was observed that the population of aphids on the top 10 cm apical twigs ranged from 1.23 to 25.56 aphids per plant. The treatment with Thiamethoxam 25 WG @ of 0.2g/liter showed a significantly lower aphid population, with only 1.23 aphids on the top 10 cm central twig per plant compared to the control. Additionally, this treatment resulted in the maximum yield of 18.73q/ha, which was superior to the other treatments. Furthermore, the treatment with Thiamethoxam 25 WG at a rate of 0.2g/liter also showed the highest net income gain of Rs. 54414/ha. The cost-benefit ratio analysis indicated that this treatment ranked first, with a B: C ratio of 1:40.63, suggesting the highest returns on investment. These findings suggest that the application of Thiamethoxam 25 WG at a rate of 0.2g/liter can effectively control aphid populations and enhance the yield and profitability of Indian mustard cultivation