Therapeutic efficacy of nanoparticles and routes of administration

[[abstract]]In modern-day medicine, nanotechnology and nanoparticles are some of the indispensable tools in disease monitoring and therapy. The term "nanomaterials" describes materials with nanoscale dimensions (<100nm) and are broadly classified into natural and synthetic nanomaterials. However, "engineered" nanomaterials have received significant attention due to their versatility. Although enormous strides have been made in research and development in the field of nanotechnology, it is often confusing for beginners to make an informed choice regarding the nanocarrier system and its potential applications. Hence, in this review, we have endeavored to briefly explain the most commonly used nanomaterials, their core properties and how surface functionalization would facilitate competent delivery of drugs or therapeutic molecules. Similarly, the suitability of carbon-based nanomaterials like CNT and QD has been discussed for targeted drug delivery and siRNA therapy. One of the biggest challenges in the formulation of drug delivery systems is fulfilling targeted/specific drug delivery, controlling drug release and preventing opsonization. Thus, a different mechanism of drug targeting, the role of suitable drug-laden nanocarrier fabrication and methods to augment drug solubility and bioavailability are discussed. Additionally, different routes of nanocarrier administration are discussed to provide greater understanding of the biological and other barriers and their impact on drug transport. The overall aim of this article is to facilitate straightforward perception of nanocarrier design, routes of various nanoparticle administration and the challenges associated with each drug delivery method

Komparative Genomik von Industriellen Mikroorganismen

Abweichender Titel nach Übersetzung der Verfasserin/des VerfassersKurzfassung Ungleich der meisten Pilze sind Schimmelpilze der Gattung Trichoderma (Hypocreales, Ascomycota) aggressive Parasiten anderer Pilze sowie effiziente Zersetzer pflanzlicher Biomasse. Obgleich Nahrungsveränderungen in der Gattung der hypocrealen Pilze gängig sind, gibt es keine Beispiele für diese umfassenden Substrat-Vielseitigkeit in Trichoderma. Viele der Trichoderma Spezies werden als Biodünger und Biofungizide verwendet; T. Reesei dient als Modellorganismus in der industriellen Produktion zellulolytischer Enzyme. Außerdem verwüsten manche opportunistische Spezies Pilzfarmen und können so als Krankheitserreger dem Menschen gefährlich werden. Aus diesem Grund ist es erforderlich die immer größere Relevanz der ubiquitären Pilzgattung Trichoderma sowohl in ihrer Biologie als auch Evolution zu verstehen. Eine vergleichende Analyse der drei ersten Genome hat ergeben, dass Mycoparasitismus eine angeborene Eigenschaft Trichodermas ist. Allerdings ist die Entwicklung anderer Eigenschaften weiterhin noch nicht entschlüsselt. Wir haben die am häufigsten vorkommenden Trichoderma Spezies ausgewählt und ihre genomische Entwicklung untersucht. Eine phylogenomische Untersuchung 23 hypocrealer Pilze (einschließlich neun Trichoderma spp. Sowie dem Verwandten Escovopsis weberi) hat ergeben, dass die Gattung Trichoderma und E. Weberi von einem gemeinsamen Vorfahren, welcher limitierte zellulolytische Fähigkeiten hatte und sich von anderen Pilzen oder Arthropoden ernährte, abstammen. Weiters litt das Escovopsis weberi Genom unter extensivem Genverlust, wodurch seine kohlehydrat-aktiven Enzyme dezimiert wurden. Die evolutionäre Analyse des Trichoderma Gens, welches für Pflanzenzellwand abbauende, kohlehydrataktive Enzyme sowie für Hilfsproteine (pcwdcazome, 122 Genfamilien) codiert basierend auf einer Genbaum/Spezies Übereinstimmung - hat bewiesen, dass die Entstehung der Gattung durch bisher unbekanntes Ausmaß an lateralem Gentransfer (lateral gene transfer, LGT) einhergegangen ist. Nahezu die Hälfte der Gene im Trichoderma pcwdcazome (47%) wurden durch LGT pflanzennaher filamentöser Pilze, welche diversen Klassen der Ascomycota angehören, erhalten, während kein LGT von anderen potentiellen Spendern beobachtet werden konnte. Zusätzlich zu der Fähigkeit sich von nicht verwandten Pilzen (wie beispielsweise Basidiomycota) zu ernähren, können wir außerdem zeigen, dass Trichoderma in der Lage ist, Endoparasitismus an einer breiten Auswahl an Ascomycota, inklusive vorhandenen LGT Spendern, zu betreiben. Dieses Phänomen konnte jedoch nicht bei E. Weberi und nur sehr selten bei anderen mycoparasitischen hypocrealean Pilzen beobachtet werden. Dementsprechend schlägt unsere Studie vor, dass LGT im Zusammenhang mit Trichodermas Fähigkeit, von taxonomisch verwandten Pilzen (genau genommen bis hin zu Adelphoparasitismus) zu schmarotzen, steht. Das könnte dazu geführt haben, dass der primär mycotrophische Pilz Trichoderma sich zu einem Pflanzenbiomasseverwerter entwickelt hat. Die Beurteilung des gesamten Proteoms bezüglich lgts bestätigt, dass diese Art von starkem LGT speziell auf das pcwdcazome zutrifft und nicht auf andere Genfamilien. Die Entwicklung Trichodermas hat in der Zeit des kreidezeitlich-Paläogenen Aussterbens vor 66 (15) Millionen Jahren stattgefunden; die Entstehung der noch vorhandenen taxonomical sections (Longibrachiatum und Trichoderma) sowie Kladen (Harzianum/Virens) geschah im Oligozän. Die Evolution der Harzianum Klade und des Bereichs der Trichoderma wurde von signifikantem Genzuwachs begleitet; der Vorfahre der Sektion Longibrachiatum jedoch durchlief rapiden Genverlust. Ankyrine sind die Gene, welche dabei am häufigsten erlangt wurden. Die evolutionäre Analyse der Ankyrin-Domänen beinhaltenen Proteine, welche im Zuge dieser Doktorarbeit durchgeführt wurde, hat gezeigt, dass sie außerdem häufig in „Orphomes“ in allen Trichoderma Spezies vorkommen. Bei etwa der Hälfte der Trichoderma ankyrome handelt es sich um „orphan“-Proteine. Die erlangten Daten, welche in dieser Dissertation präsentiert werden, geben Einblick in die evolutionären Mechanismen des Mykoparasiten Trichoderma und dessen Entwicklung zu einem Generalisten.Unlike most other fungi, molds of the genus Trichoderma (Hypocreales, Ascomycota) are aggressive parasites of other fungi and efficient decomposers of plant biomass. Although nutritional shifts are common among hypocrealean fungi, there are no examples of such broad substrate versatility as that observed in Trichoderma. Many Trichoderma species are used as biofertilizers and biofungicides, and T. Reesei is the model organism for industrial production of cellulolytic enzymes. In addition, some highly opportunistic species devastate mushroom farms and become pathogens of humans. Thus, the growing importance of the ubiquitous fungal genus Trichoderma requires understanding its biology and evolution. A comparative analysis of the first three genomes revealed mycoparasitism as an innate feature of Trichoderma. However, the evolution of other traits remained not understood. We selected most commonly occurring Trichoderma species and studied the evolution of their genomes. A phylogenomic analysis of 23 hypocrealean fungi (including nine Trichoderma spp. And the related Escovopsis weberi) revealed that the genus Trichoderma and E. Weberi has evolved from an ancestor with limited cellulolytic capability that fed on either fungi or arthropods. Further, the genome of Escovopsis weberi has undergone extensive gene loss and became depleted in carbohydrate-active enzymes. The evolutionary analysis of Trichoderma genes encoding plant cell wall-degrading carbohydrate-active enzymes and auxiliary proteins (pcwdcazome, 122 gene families) based on a gene tree / species tree reconciliation demonstrated that the formation of the genus was accompanied by an unprecedented extent of lateral gene transfer (LGT). Nearly one-half of the genes in Trichoderma pcwdcazome (47%) were obtained via LGT from plant-associated filamentous fungi belonging to different classes of Ascomycota, while no LGT was observed from other potential donors. In addition to the ability to feed on unrelated fungi (such as Basidiomycota), we also showed that Trichoderma is capable of endoparasitism on a broad range of Ascomycota, including extant LGT donors. This phenomenon was not observed in E. Weberi and rarely in other mycoparasitic hypocrealean fungi. Thus, our study suggests that LGT is linked to the ability of Trichoderma to parasitize taxonomically related fungi (up to adelphoparasitism in strict sense). This may have allowed primarily mycotrophic Trichoderma fungi to evolve into decomposers of plant biomass. The whole proteome LGT assessment confirmed this kind of massive LGT is specific for pcwdcazome and not to any other gene families. Trichoderma evolved in the time of the Cretaceous-Palaeogene extinction event 66 (15) Mya, but the formation of extant sections (Longibrachiatum and Trichoderma) or clades (Harzianum/Virens) happened in the Oligocene. The evolution of the Harzianum clade and section Trichoderma was accompanied by significant gene gain, but the ancestor of section Longibrachiatum experienced rapid gene loss. Ankyrins are amongst the largest number of genes gained. The evolutionary analysis of ankyrin domain-containing proteins performed in the course of this dissertation revealed that they are also frequent in orphomes of all Trichoderma species. About one half of Trichoderma ankyrome are orphan proteins. The data presented in this dissertation offer insights into the evolutionary mechanisms of a mycoparasite Trichoderma towards becoming a generalist28

Evolution of mycoparasitism in Hypocreales fungi through phylogenomic approach

A profound affinity to mycotrophy, i.e. the ability to antagonize, parasitize or even kill a broad range of other fungi including closely related Ascomycota, remains to be the major ecological descriptor of the genus Trichoderma. The pilot phylogenomic analysis of the first three genomes of Trichodema, T. atroviride, T. reesei and T. virens, showed that T. atroviride most closely resembles the ancestral state of the genus, while T. reesei is the most derived taxon from these three. In this thesis, we present the first genus-wide phylogenomics of the genus Trichoderma combining the previously available materials with the data from the seven newly Trichoderma sequenced genomes from T. harzianum, T. guizhouense NJAU 4742, T. asperellum, T. longibrachiatum, T. parareesei C.P.K. 717, T. -afroharzianum- nom. prov. TUCIM 4803 and T. citrinoviride IMI 232088. We have retrieved, manually curated and aligned 100 orthologous proteins from 24 Hypocreales genomes that are currently available. A multi-gene maximum likelihood phylogram is created with MSA constituting 47,655 amino acid residues. This analysis of 24 Hypocreales genomes allowed us to detect the relatively ancient origin of the genus that essentially predates the divergence time for numerous families within the order. Simultaneously, evolutionary position of Escovopsis weberi CC031208-10, a parasite of fungal gardens cultivated by leaf-cutting ants of tribe Attini, namely leaf-cutting ants (Atta and Acromyrmex) is also revealed. We have also retrieved, manually curated and aligned 100 transcripts from 18 of the 24 Hypocrales genomes and created a maximum likelihood phylogram to compare the topologies with our protein phylogram. The transcripts phylogram is based on a MSA constituting 102,317 nucleic acids. Random selection of highly conserved 27 genes out of the 100 transcripts MSA of 18 genomes, followed by single-gene phylogenetic analysis involving 19 Hypocreales, revealed the evolutionary position of recently sequenced genome; Trichoderma hamatum GD 12. Ecophysiological studies are carried out to study and compare opportunistic, mycotrophic and mycoparasitic capabilities among Trichoderma species and also with species of related genera from the family Hypocreaceae, such as Escovopsis weberi. Protocrea pallida, Emericellopsis alkaline, Hypomyces aurantiacus and Simplicillium sp. We demonstrate the unique combination of ecological versatility and high environmental opportunism of the genus Trichoderma that probably is the major feature that distinguishes these fungi from next genetic neighbors

Ionic liquids as alternative solvents for energy conservation and environmental engineering

Because of industrialization and modernization, phenomenal changes have taken place in almost all spheres of life. Consequently, the consumption of energy resources and the cases of environmental hazards have risen to an unprecedentedly high level. A development model with due consideration to nature and an efficient utilization of energy sources has become the need of the hour, in order to ensure a sustainable balance between the environmental and technological needs. Recent studies have identified the suitability of ionic liquids (ILs), often labeled as ‘green solvents’, in the efficient utilization of energy resources and activities such as bio-extraction, pollution control, CO2 capture, waste management etc. in an environmentally friendly manner. The advent of magnetic ionic liquids (MILs) and deep eutectic solvents (DESs) have opened possibilities for a circular economic approach in this filed. This review intends to analyze the environmental and energy wise consumption of a wide variety of ionic liquids and their potential towards future.</jats:p

Help-seeking behaviour of parents of children with hearing loss in India: a qualitative analysis

The age of identification of hearing loss in children is highly influenced by the hearing help seeking behaviour of their parents, particularly in countries without universal newborn hearing screening programs. In this study, an attempt was made to identify the factors associated with help seeking behaviour in parents of children with hearing loss, and the relationship of such factors with the age of identification of hearing loss. Focus group discussions based on the framework of health belief model were carried out. The discussions were transcribed and the transcripts were thematically analysed. Participants were 35 parents of children with hearing loss from the state of Karnataka in India. The findings revealed 30 factors related to their awareness about hearing loss, geographical location, socio-economic status, family, and society. The factors differed between early and late help seekers. Awareness, accessibility, and affordability are the key factors that influenced the hearing help seeking behaviour of the participants. Effective public awareness programs, newborn hearing screening programs, and provisions to make hearing healthcare affordable to all can reduce the age of identification of paediatric hearing loss in India.</p

Ionic liquids as alternative solvents for energy conservation and environmental engineering

Because of industrialization and modernization, phenomenal changes have taken place in almost all spheres of life. Consequently, the consumption of energy resources and the cases of environmental hazards have risen to an unprecedentedly high level. A development model with due consideration to nature and an efficient utilization of energy sources has become the need of the hour, in order to ensure a sustainable balance between the environmental and technological needs. Recent studies have identified the suitability of ionic liquids (ILs), often labeled as ‘green solvents’, in the efficient utilization of energy resources and activities such as bio-extraction, pollution control, CO2 capture, waste management etc. in an environmentally friendly manner. The advent of magnetic ionic liquids (MILs) and deep eutectic solvents (DESs) have opened possibilities for a circular economic approach in this filed. This review intends to analyze the environmental and energy wise consumption of a wide variety of ionic liquids and their potential towards future

Influence of Alignment Strategies and Consonant Acoustic Features on Laterality Index in Dichotic Testing in Indian Languages

Abstract Background The right ear advantage (REA) observed for dichotic CV (DCV) testing in Indian languages is seen to be smaller compared with the observations in several studies in English and other languages. Purpose The present study aims to explore whether the differences in the temporal alignment of consonant–vowel (CV) stimuli used for the dichotic task is a contributing factor that can explain the smaller REAs observed in Indian languages. Research Design The study compared the laterality index (LI) values between DCV test results obtained using CV stimuli that were temporally aligned at the acoustic onset versus the burst onset, with 0 milliseconds lag between the right and left ears. Study Sample A total of 50 right-handed individuals (native speakers of Kannada language) in the age range of 17 to 30 years with normal hearing sensitivity participated in the study. Data Collection and Analysis The participants' responses to the two sets of DCV stimuli were recorded and compared. LI was calculated for the overall scores as well as for specific voiced and unvoiced segment combinations. To test the reliability of the findings, 10 of the participants were re-tested using the same stimuli and the data were checked for reliability. Results The overall LI was 15.1% for the stimuli temporally aligned at the burst onset, whereas it was 5.7% for the stimuli temporally aligned at the acoustic onset. The difference in LI was not significant between the alignment conditions for unvoiced–unvoiced and voiced–voiced CV combinations, but this difference was significant for the unvoiced–voiced and voiced–unvoiced CV combinations. Comparing test and re-test scores showed good reliability. Conclusion The results support our hypothesis that smaller REA observed in DCV task in Indian languages was due to the temporal alignment of CV stimuli. In the acoustic-onset-aligned condition, presenting pairs contrasting in the voicing feature tends to cancel out a relative ear advantage.</jats:p