Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that triggers senescence. To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced staining for β-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.

/pdf/extension-of-life-span-by-introduction-of-telomerase-into-4ucjiz7vl1.pdf

Extension of life-span by introduction of telomerase into normal human cells

Pedagosko i psiholosko testiranje i procjenjivanje spadaju među najvažnije doprinose znanosti o ponasanju nasem drustvu i pružaju temeljna i znacajna poboljsanja u odnosu na ranije postupke. Iako se ne može ustvrditi da su svi testovi dovoljno usavrseni niti da su sva testiranja razborita i korisna, postoji velika kolicina informacija koje ukazuju na ucinkovitost kvalitetnih instrumenata u onim situacijama u kojima je njihovo koristenje potkrijepljeno validacijskim podacima. Pravilna upotreba testova može dovesti do boljih odluka o pojedincima i programima nego sto bi to bio slucaj bez njihovog koristenja, a također i ukazati na put za siri i pravedniji pristup obrazovanju i zaposljavanju. Međutim, losa upotreba testova može dovesti do zamjetne stete nanesene ispitanicima i drugim sudionicima u procesu donosenja odluka na temelju testovnih podataka. Cilj Standarda je promoviranje kvalitetne i eticne upotrebe testova te uspostavljanje osnovice za ocjenu kvalitete postupaka testiranja. Svrha objavljivanja Standarda je uspostavljanje kriterija za evaluaciju testova, provedbe testiranja i posljedica upotrebe testova. Iako bi evaluacija prikladnosti testa ili njegove primjene trebala ovisiti prvenstveno o strucnim misljenjima, Standardi pružaju okvir koji osigurava obuhvacanje svih relevantnih pitanja. Bilo bi poželjno da svi autori, sponzori, nakladnici i korisnici profesionalnih testova usvoje Standarde te da poticu druge da ih također prihvate.

Standards for educational and psychological testing

Catalytic protein subunits of telomerase from the ciliate Euplotes aediculatus and the yeast Saccharomyces cerevisiae contain reverse transcriptase motifs. Here the homologous genes from the fission yeast Schizosaccharomyces pombe and human are identified. Disruption of the S. pombe gene resulted in telomere shortening and senescence, and expression of mRNA from the human gene correlated with telomerase activity in cell lines. Sequence comparisons placed the telomerase proteins in the reverse transcriptase family but revealed hallmarks that distinguish them from retroviral and retrotransposon relatives. Thus, the proposed telomerase catalytic subunits are phylogenetically conserved and represent a deep branch in the evolution of reverse transcriptases.

https://science.sciencemag.org/content/sci/277/5328/955.full.pdf

Telomerase catalytic subunit homologs from fission yeast and human

https://courses.washington.edu/gs466/readings/meyerson.pdf

hEST2, the Putative Human Telomerase Catalytic Subunit Gene, Is Up-Regulated in Tumor Cells and during Immortalization

Section I: Anatomy Surgical Anatomy of the Retroperitoneum, Kidneys, and Ureters Anatomy of the Lower Urinary Tract and Male Genitalia Section II: Clinical Decision Making Evaluation of the Urologic Patient: History, Physical Examination, and Urinalysis Urinary Tract Imaging: Basic Principles Outcomes Research Section III: Basics of Urologic Surgery Basic Instrumentation and Cystoscopy Basics of Laparoscopic Urologic Surgery Section IV: Infections and Inflammation Infections of the Urinary Tract-A. Schaeffer Inflammatory Conditions of the Male Genitourinary Tract Interstitial Cystitis and Related Disorders Sexually Transmitted and Associated Diseases Urological Implications of AIDS and Related Conditions Cutaneous Diseases of the External Genitalia Tuberculosis and Other Opportunistic Infections of the Genitourinary System Section V: Molecular and Cellular Biology Basic Principles of Immunology Molecular Genetics and Cancer Biology Tissue Engineering Perspectives for Reconstructive Surgery Section VI: Reproductive and Sexual Function Male Reproductive Physiology Male Infertility Surgical Management of Male Infertility Physiology of Erectile Dysfunction: Pathophysiology, Evaluation, Nonsurgical Management Epidemiology, Evaluation, and Nonsurgical Management of Erectile Dysfunction Prosthetic Surgery for Erectile Dysfunction Vascular Surgery for Erectile Dysfunction Peyronie's Disease Priapism Androgen Deficiency in the Aging Male Female Sexual Function and Dysfunction Section VII: Male Genitalia Neoplasms of the Testis Surgery of Testicular Tumors Tumors of the Penis Surgery of Penile and Urethral Carcinoma Surgery of the Penis and Urethra Surgery of the Scrotum and Seminal Vesicles Section VIII: Renal Physiology and Pathophysiology Renal Physiology and Pathophysiology Renovascular Hypertension Section IX: Upper Urinary Tract Obstruction and Trauma Pathophysiology of Obstruction Management of Upper Urinary Tract Obstruction Upper Urinary Tract Trauma Section X: Renal Failure and Transplantation Renal Transplantation Etiology, Pathogenesis, and Management of Renal Failure Section XI: Urinary Lithiasis and Endourology Urinary Lithiasis: Etiology, Epidemiology, and Pathophysiology Evaluation and Medical Management of Urinary Lithiasis Surgical Management of Upper Urinary Tract Calculi Ureteroscopy and Retrograde Ureteral Access Percutaneous Approaches to the Upper Urinary Tract Section XII: Neoplasms of the Upper Urinary Tract Renal Tumors Urothelial Tumors of the Upper Urinary Tract Urothelial Tumors of the Renal Pelvis and Ureter Open Surgery of the Kidney Laparoscopic Surgery of the Kidney Ablative Therapy for Renal Tumors Section XIII: The Adrenals Pathophysiology, Evaluation, and Medical Management of Adrenal Disorders Surgery of the Adrenals Section XIV: Urine Transport, Storage, and Emptying Physiology and Pharmacology of the Renal Pelvis and Ureter Physiology and Pharmacology of the Bladder and Urethra Pathophysiology, Categorization, and Management of Voiding Dysfunction Urodynamic and Video dynamic Evaluation of Voiding Dysfunction Neuromuscular Dysfunction of the Lower Urinary Tract Urinary Incontinence: Epidemiology, Pathophysiology, Evaluation, and Overview of Management The Overactive Bladder Pharmacologic Management of Storage and Emptying Failure Conservative Management of Urinary Incontinence: Behavioral and Pelvic Floor Therapy, Urethral and Pelvic Devices Electrical Stimulation and Neuromodulation in Storage and Emptying Failure Retropubic Suspension Surgery for Incontinence in Women Vaginal Reconstructive Surgery for Sphincteric Incontinence Pubovaginal Slings Tension-Free Vaginal Tape Procedures Injection Therapy for Urinary Incontinence Additional Treatment for Storage and Emptying Failure Geriatric Voiding Dysfunction and Urinary Incontinence Urinary Tract Fistulae Bladder and Urethral Diverticula Surgical Procedures for Sphincteric Incontinence in the Male: The Artificial Genitourinary Sphincter Perineal Sling Procedures Section XV: Bladder Lower Genitourinary Calculi and Trauma Urothelial Tumors of the Bladder Management of Superficial Bladder Cancer Management of Metastatic and Invasive Bladder Cancer Surgery of Bladder Cancer Laparoscopic Bladder Surgery Use of Intestinal Segments in Urinary Diversion Cutaneous Continent Urinary Diversion Orthotopic Urinary Diversion Genital and Lower Urinary Tract Trauma Lower Urinary Tract Calculi Section XVI: Prostate Molecular Biology, Endocrinology, and Physiology of the Prostate and Seminal Vesicles Etiology, Pathophysiology, and Epidemiology of Benign Prostatic Hyperplasia Natural History, Evaluation, and Nonsurgical Management of Benign Prostatic Hyperplasia Minimally Invasive and Endoscopic Management of Benign Prostatic Hyperplasia Retropubic and Superpubic Open Radical Prostatectomy Epidemiology, Etiology, and Prevention of Prostate Cancer Pathology of Prostatic Neoplasms Ultrasonography and Biopsy of the Prostate Tumor Markers in Prostate Cancer Early Detection, Diagnosis, and Staging of Prostate Cancer Definitive Therapy of Localized Prostate Cancer: Outcomes Expectant Management of Prostate Cancer Anatomic Retrograde Retropubic Prostatectomy Radical Perineal Prostatectomy Laparoscopic and Robotic Radical Prostatectomy and Pelvic Lymphadenectomy Radiation Therapy for Prostate Cancer Cryotherapy of Prostate Cancer Treatment of Locally Advanced Prostate Cancer Management of Rising Prostate-Specific Antigen after Definitive Therapy Hormonal Therapy for Prostate Cancer Management of Hormone-Resistant Prostate Cancer Section XVII: Pediatric Urology Normal and Anomalous Development of the Urinary Tract Renal Function in the Fetus Congenital Obstructive Uropathy Perinatal Urology Evaluation of Pediatric Urologic Patient Renal Disease in Childhood Urinary Tract Infections in Infants and Children Anomalies of the Kidney Renal Dysplasia and Cystic Disease of Kidney Anomalies and Surgery of the Ureteropelvic Junction Ectopic Ureter Vesicoureteral Reflux Prune-Belly Syndrome Exstrophy and Epispadias Complex Surgical Technique for One-Stage Exstrophy Reconstruction Bladder Anomalies in Children Posterior Urethral Valves and Other Urethral Anomalies Voiding Dysfunction in Children: Neurogenic and Non-neurogenic Urinary Tract Reconstruction Hypospadias Abnormalities of External Genitalia in Boys Abnormalities of Testis and Scrotum: Surgical Management Sexual Differentiation: Normal and Abnormal Surgical Management of Intersex Pediatric Oncology Pediatric Endourology and Laparoscopy Pediatric Genitourinary Trauma

Campbell-Walsh urology

The primary determinant for telomere replication is the enzyme telomerase, responsible for elongating the G-rich strand of the telomere. The only component of this enzyme that has been identified in Saccharomyces cerevisiae is the TLC1 gene, encoding the telomerase RNA subunit. However, a yeast strain defective for the EST1 gene exhibits the same phenotypes (progressively shorter telomeres and a senescence phenotype) as a strain deleted for TLC1, suggesting that EST1 encodes either a component of telomerase or some other factor essential for telomerase function. We designed a multitiered screen that led to the isolation of 22 mutants that display the same phenotypes as est1 and tlc1 mutant strains. These mutations mapped to four complementation groups: the previously identified EST1 gene and three additional genes, called EST2, EST3 and EST4. Cloning of the EST2 gene demonstrated that it encodes a large, extremely basic novel protein with no motifs that provide clues as to function. Epistasis analysis indicated that the four EST genes function in the same pathway for telomere replication as defined by the TLC1 gene, suggesting that the EST genes encode either components of telomerase or factors that positively regulate telomerase activity.

https://www.genetics.org/content/genetics/144/4/1399.full.pdf

Senescence Mutants of Saccharomyces cerevisiae With a Defect in Telomere Replication Identify Three Additional EST Genes

Crowd-Sourced Assessment of Technical Skills: a novel method to evaluate surgical performance

Methodologies for establishing validity in surgical simulation studies.

Use of 3-Dimensional Printing Technology and Silicone Modeling in Surgical Simulation: Development and Face Validation in Pediatric Laparoscopic Pyeloplasty

Thomas S. Lendvay

Papers

Senescence Mutants of Saccharomyces cerevisiae With a Defect in Telomere Replication Identify Three Additional EST Genes

Crowd-Sourced Assessment of Technical Skills: a novel method to evaluate surgical performance

Methodologies for establishing validity in surgical simulation studies.

Use of 3-Dimensional Printing Technology and Silicone Modeling in Surgical Simulation: Development and Face Validation in Pediatric Laparoscopic Pyeloplasty

The tuberous sclerosis complex and its highly variable manifestations.