Salman Akhtar

Os carcinog neos transformam-se em metabolitos electrof licos, ligam-se ao ADN e causam cancro atrav s da ativa o metab lica, desintoxica o, angiog nese e met stases. As isozimas CYP s o alvos terap uticos no cancro da mama induzido por DBP. LBVS, docking molecular, simula es MD e estudos in vitro centraram-se em CYP1A1, 1A2 e 1B1. LBVS identificou hits, refinou-os utilizando os filtros RO5 e ADMET de Lipinski e acoplou-os utilizando AutoDock4. CHEMBL1, CHEMBL2 e CHEMBL3 mostraram afinidades de liga o superiores a ANF. A estabilidade foi confirmada atrav s de simula es MD. A filtragem ADMET produziu resultados n o t xicos, com ANA8430692 e ANA7923580 a exibirem uma estabilidade ptima. A din mica molecular e os ensaios de inibi o enzim tica validaram o seu potencial como inibidores do CYP. Os an logos concebidos ANA6917483, ANA8430692 e ANA6451816 apresentaram fortes padr es de liga o e intera o, sugerindo potencial anticancer geno. Este estudo melhora a nossa compreens o da preven o do cancro da mama induzida pelo DBP.

Karzinogene wandeln sich in elektrophile Metaboliten um, binden an die DNA und verursachen Krebs durch Stoffwechselaktivierung, Entgiftung, Angiogenese und Metastasierung. CYP-Isoenzyme sind therapeutische Ziele bei DBP-induziertem Brustkrebs. LBVS, molekulares Docking, MD-Simulationen und In-vitro-Studien konzentrierten sich auf CYP1A1, 1A2 und 1B1. LBVS identifizierte Treffer, verfeinerte sie mit Lipinskis RO5 und ADMET-Filtern und dockte sie mit AutoDock4 an. CHEMBL1, CHEMBL2 und CHEMBL3 zeigten eine hohe Bindungsaffinit t zu ANF. Die Stabilit t wurde durch MD-Simulationen best tigt. Die ADMET-Filterung ergab ungiftige Treffer, wobei ANA8430692 und ANA7923580 eine optimale Stabilit t aufwiesen. Molekulardynamik- und Enzyminhibitionstests best tigten ihr Potenzial als CYP-Inhibitoren. Die Analoga ANA6917483, ANA8430692 und ANA6451816 zeigten starke Bindungs- und Interaktionsmuster, die auf ein Potenzial zur Krebsbek mpfung schlie en lassen. Diese Studie verbessert unser Verst ndnis der DBP-induzierten Pr vention von Brustkrebs.

Substancje rakotw rcze przeksztalcają się w elektrofilowe metabolity, wiążą się z DNA i powodują raka poprzez aktywację metaboliczną, detoksykację, angiogenezę i przerzuty. Izozymy CYP są celami terapeutycznymi w raku sutka wywolanym przez DBP. LBVS, dokowanie molekularne, symulacje MD i badania in vitro skupily się na CYP1A1, 1A2 i 1B1. LBVS zidentyfikowal trafienia, udoskonalil je za pomocą filtr w RO5 i ADMET Lipinskiego i zadokowal je za pomocą AutoDock4. CHEMBL1, CHEMBL2 i CHEMBL3 wykazaly lepsze powinowactwo wiązania do ANF. Stabilnośc zostala potwierdzona za pomocą symulacji MD. Filtrowanie ADMET dalo nietoksyczne trafienia, z ANA8430692 i ANA7923580 wykazującymi optymalną stabilnośc. Dynamika molekularna i testy inhibicji enzym w potwierdzily ich potencjal jako inhibitor w CYP. Zaprojektowane analogi ANA6917483, ANA8430692 i ANA6451816 wykazywaly silne wzorce wiązania i interakcji, sugerując potencjal przeciwnowotworowy. Badanie to poglębia naszą wiedzę na temat zapobiegania rakowi sutka wywolanemu przez DBP.

Le sostanze cancerogene si trasformano in metaboliti elettrofili, si legano al DNA e causano il cancro attraverso l'attivazione metabolica, la disintossicazione, l'angiogenesi e le metastasi. Gli isozimi CYP sono bersagli terapeutici nel cancro mammario indotto da DBP. L'LBVS, il docking molecolare, le simulazioni MD e gli studi in vitro si sono concentrati sui CYP1A1, 1A2 e 1B1. L'LBVS ha identificato gli hit, li ha raffinati usando i filtri RO5 e ADMET di Lipinski e li ha agganciati usando AutoDock4. CHEMBL1, CHEMBL2 e CHEMBL3 hanno mostrato un'affinit di legame superiore con ANF. La stabilit stata confermata tramite simulazioni MD. Il filtraggio ADMET ha prodotto risultati non tossici, con ANA8430692 e ANA7923580 che hanno mostrato una stabilit ottimale. La dinamica molecolare e i saggi di inibizione enzimatica hanno convalidato il loro potenziale come inibitori del CYP. Gli analoghi progettati ANA6917483, ANA8430692 e ANA6451816 hanno mostrato forti modelli di legame e interazione, suggerendo un potenziale antitumorale. Questo studio migliora la nostra comprensione della prevenzione del cancro mammario indotta dal DBP.

Les substances canc rig nes se transforment en m tabolites lectrophiles, se lient l'ADN et provoquent le cancer par le biais de l'activation m tabolique, de la d toxification, de l'angiogen se et des m tastases. Les isozymes CYP sont des cibles th rapeutiques dans le cancer mammaire induit par le DBP. LBVS, l'amarrage mol culaire, les simulations MD et les tudes in vitro se sont concentr s sur CYP1A1, 1A2 et 1B1. LBVS a identifi des hits, les a affin s en utilisant les filtres RO5 et ADMET de Lipinski et les a amarr s l'aide d'AutoDock4. CHEMBL1, CHEMBL2 et CHEMBL3 ont montr des affinit s de liaison sup rieures au FNA. La stabilit a t confirm e par des simulations MD. Le filtrage ADMET a donn des r sultats non toxiques, ANA8430692 et ANA7923580 pr sentant une stabilit optimale. Des essais de dynamique mol culaire et d'inhibition enzymatique ont valid leur potentiel en tant qu'inhibiteurs du CYP. Les analogues con us ANA6917483, ANA8430692 et ANA6451816 ont pr sent des mod les de liaison et d'interaction forts, sugg rant un potentiel anticanc reux. Cette tude nous permet de mieux comprendre la pr vention du cancer mammaire induite par le DBP.

Mit Hilfe der subtraktiven Proteomik und der reversen Vakzinologie wurde ein chim rer Multiepitop-Impfstoff gegen Melioidose entwickelt, eine schwere Infektionskrankheit, die durch das multiresistente Bakterium Burkholderia pseudomallei verursacht wird. Aus 21 nicht redundanten Erregerproteomen wurden vier Proteine als Impfstoffkandidaten ausgew hlt, und zwar auf der Grundlage von Essentialit t, Virulenz, Nicht-Homologie zum Menschen, struktureller Verf gbarkeit, subzellul rer Lokalisierung und Antigenit t. Die Epitope des Haupthistokompatibilit tskomplexes der Klassen I und II sowie der B-Zellen wurden vorhergesagt und auf Immunogenit t, L slichkeit, Allergenit t und Hydrophilie untersucht. Unter Verwendung der Epitope, Adjuvantien, Linker und PADRE-Sequenzen wurde ein chim rer Impfstoff konstruiert. Docking- und Molekulardynamiksimulationen best tigten die Wechselwirkungen zwischen HLA-Allelen und TLR4, was auf das Potenzial zur Ausl sung einer Immunantwort hindeutet und den Nutzen von computergest tzten Werkzeugen bei der Entwicklung von Impfstoffen gegen B. pseudomallei unter Beweis stellt.

Proteomika subtraktywna i odwrotna wakcynologia zostaly wykorzystane do zaprojektowania chimerycznej szczepionki wieloepitopowej przeciwko melioidozie, ciężkiej chorobie zakaźnej wywolywanej przez wielolekooporną bakterię Burkholderia pseudomallei. Spośr d 21 nieredundantnych proteom w patogen w, cztery bialka zostaly wybrane jako kandydaci na szczepionki w oparciu o istotnośc, zjadliwośc, brak homologii z ludźmi, dostępnośc strukturalną, lokalizację subkom rkową i antygenowośc. Przewidziano epitopy gl wnego kompleksu zgodności tkankowej klasy I, II i kom rek B oraz oceniono je pod kątem immunogenności, rozpuszczalności, alergenności i hydrofilności. Skonstruowano szczepionkę chimeryczną przy użyciu epitop w, adiuwant w, lącznik w i sekwencji PADRE. Symulacje dokowania i dynamiki molekularnej potwierdzily interakcje między allelami HLA i TLR4, wskazując na potencjal do wywolania odpowiedzi immunologicznej, demonstrując użytecznośc narzędzi obliczeniowych w opracowywaniu szczepionek przeciwko B. pseudomallei.

La proteomica sottrattiva e la vaccinologia inversa sono state impiegate per progettare un vaccino chimerico multi-epitopo contro la melioidosi, una grave malattia infettiva causata dal batterio multiresistente Burkholderia pseudomallei. Da 21 proteomi non ridondanti del patogeno, sono state selezionate quattro proteine come candidate al vaccino in base a essenzialit , virulenza, non omologia con l'uomo, disponibilit strutturale, localizzazione subcellulare e antigenicit . Gli epitopi del complesso di istocompatibilit maggiore di classe I, II e delle cellule B sono stati previsti e valutati per immunogenicit , solubilit , allergenicit e idrofilia. stato costruito un vaccino chimerico utilizzando gli epitopi, gli adiuvanti, i linker e le sequenze PADRE. Le simulazioni di docking e di dinamica molecolare hanno confermato le interazioni tra gli alleli HLA e il TLR4, indicando il potenziale di suscitare una risposta immunitaria, dimostrando l'utilit degli strumenti computazionali nello sviluppo di vaccini contro B. pseudomallei.

La prot omique soustractive et la vaccinologie inverse ont t utilis es pour concevoir un vaccin chim rique pitopes multiples contre la m lio dose, une maladie infectieuse grave caus e par la bact rie multir sistante Burkholderia pseudomallei. partir de 21 prot omes pathog nes non redondants, quatre prot ines ont t s lectionn es comme candidats vaccins sur la base de leur essentialit , de leur virulence, de leur non-homologie avec l'homme, de leur disponibilit structurelle, de leur localisation subcellulaire et de leur antig nicit . Les pitopes du complexe majeur d'histocompatibilit de classe I, II et des cellules B ont t pr dits et valu s en termes d'immunog nicit , de solubilit , d'allerg nicit et d'hydrophilie. Un vaccin chim rique a t construit en utilisant les pitopes, les adjuvants, les linkers et les s quences PADRE. Les simulations de docking et de dynamique mol culaire ont confirm les interactions entre les all les HLA et TLR4, indiquant le potentiel de d clenchement d'une r ponse immunitaire, d montrant l'utilit des outils informatiques dans le d veloppement de vaccins contre B. pseudomallei.

A prote mica subtractiva e a vacinologia inversa foram utilizadas para conceber uma vacina quim rica de m ltiplos ep topos contra a melioidose, uma doen a infecciosa grave causada pela bact ria multirresistente Burkholderia pseudomallei. A partir de 21 proteomas n o redundantes de agentes patog nicos, foram selecionadas quatro prote nas como candidatas a vacinas com base na essencialidade, virul ncia, n o-homologia com humanos, disponibilidade estrutural, localiza o subcelular e antigenicidade. Os principais complexos de histocompatibilidade de classe I, II e ep topos de c lulas B foram previstos e avaliados quanto imunogenicidade, solubilidade, alergenicidade e hidrofilicidade. Foi constru da uma vacina quim rica utilizando os ep topos, os adjuvantes, os ligantes e as sequ ncias PADRE. As simula es de docking e din mica molecular confirmaram intera es entre alelos HLA e TLR4, indicando o potencial para provocar uma resposta imunit ria, demonstrando a utilidade de ferramentas computacionais no desenvolvimento de vacinas contra B. pseudomallei.

Carcinogens transform into electrophilic metabolites, bind to DNA, and cause cancer via metabolic activation, detoxification, angiogenesis, and metastasis. CYP isozymes are therapeutic targets in DBP-induced mammary cancer. LBVS, molecular docking, MD simulations, and in vitro studies have focused on CYP1A1, 1A2, and 1B1. LBVS identified hits, refined using Lipinski's RO5 and ADMET filters, and docked them using AutoDock4. CHEMBL1, CHEMBL2, and CHEMBL3 showed superior binding affinities to ANF. The stability was confirmed via MD simulations. ADMET filtering yielded nontoxic hits, with ANA8430692 and ANA7923580 exhibiting optimal stability. Molecular dynamics and enzyme inhibition assays validated their potential as CYP inhibitors. Designed analogs ANA6917483, ANA8430692, and ANA6451816 displayed strong binding and interaction patterns, suggesting anticancer potential. This study enhances our understanding of the DBP-induced prevention of mammary cancer.

In Short: Private Notes of a Psychoanalyst is wise, uplifting and inspiring. Salman Akhtar brings his talent for poetic literature to gift us 111 pithy ‘proto-essays’ on a wide range of subjects. His meditations touch upon mental health, humor, death, animals, Freud, religion, children, and so much more. He imparts his advice with the lightest of touches, willing you to partake, consider, and refine his offerings. His aim: to further the cause and message of his beloved psychoanalysis.

Salman Akhtar is a Professor of Psychiatry, a Training and Supervising Analyst, a member of numerous editorial boards, winner of many awards, including the highly prestigious Sigourney Award, a writer of several hundred articles, a poet, and the author or editor of over one hundred books. A modern-day Renaissance man, his elegant writing is simultaneously scholarly and literary and brings a light touch to profound material. Phoenix Publishing House is proud to present his most inspiring works in a stunning ten-volume hardback set, fit to grace the shelves of collectors and libraries with its high-quality finish. Volume I: Character Pathology Volume II: Metapsychology and Fantasy Volume III: Negative Emotions and Attitudes Volume IV: Positive Emotions and Attitudes Volume V: Therapeutic Technique Volume VI: Immigration and Exile Volume VII: Psychoanalysis and Culture Volume VIII: Psychic Development Volume IX: Death, Writing, and Other Topics Volume X: Book Reviews, Forewords, and Commentaries

Tautly stretched over the chasm between idolization and iconoclasm, restraint and audacity, and the man-animal distinction, the poems contained in this book evoke scintillating images and garden- fresh metaphors. Parrots that live on Mount Everest, tigers who swallow poets, fishless oceans, ill-tempered camels, and sparrows of memory coexist in its pages with pancakes of platitudes, the Great Mountain of Fear, a starved Bedouin who feels enormous guilt for being hungry, the change in the direction of toes with age, and the one-eyed blacksmith of time. Never has magical surrealism cloaked existential truths better in poetry.

Salman Akhtar presents three rich essays brimming with psychoanalytic theory on personality development and how such knowledge enhances treatment. Essay 1 starts at the earliest infancy and takes the reader all along the path past adolescence. It addresses key developmental landmarks, including: - Establishing a satisfactory parental bond - Moving towards autonomy and independence - Acquiring a moral sense - Consolidating identity Essay 2 picks up after adolescence. It addresses the psychosocial challenges characteristic of young adulthood, midlife, and old age, such as: - Assuming the role of a wage-earner and 'house-holder' - Enjoying sex, love, and marriage - Downsizing and retiring from one's job - Dealing with the deaths of friends and family and facing one's own mortality Essay 3 builds upon the theory that has gone before and examines how a deepened understanding of psychic development can inform the clinician's approach. With an emphasis on development as a lifelong process, this essay provides clear guidelines for facilitating such growth, including: - Creating psychic space for thinking - Helping the patient find words for inner experiences - Validating the patient's reality - Enhancing the sense of personal agency in the patient. The complex tapestry woven by these three essays is extended by a prologue and an epilogue. The prologue opens with the 'pre-self' – events before birth that impact on who we become. The epilogue discusses the 'post-self' – how we 'live on' as memories held by those who knew us. In Leaps and Bounds deepens the understanding of the nuances of human development. It is key reading for practising and trainee psychoanalysts and psychoanalytic psychotherapists to enhance their clinical practice. It is highly recommended for all enquiring minds looking to expand their knowledge of what makes us who we are.