Como crear calendario

Por favor creen su calendario en google (pueden entrar directamente desde gmail, picandole en el tab a la izq arriba que dice calendar).
Al accesar, presionen añadir en la barra de la izq abajo (abajo del minicalendario de la izq y arriba de donde dice mis calendarios) y seleccionar añadir un calendario nuevo. Pongale nombre (su nombre) y si quieren descripcion. Agreguen en la parte de abajo (compartir) mi nombre (correo), el de Vilma y el de Magali. Piquenle en crear calendario. Luego presionen el cuadro de la hora en que esten del calendario grande nuevo creado, pongan su nombre personal en evento y acepten. Se creara el evento. Al picarle nuevamente dos veces pueden editarlo, picandole en cuando y poniendo repetir diaro (o semanalmente, etc). Repetir hasta completar su horario. Recuerden compartilo con nosotros tres o mas gente si lo desean.

Deshonor para el laboratorio!!!

Calificaciones examen de alumnos de doctorado paper estadistica (el que esta señalado un poco mas abajo en el blog)
En escala 1 a 10

Franz 2.5
Gustavo 0
Varenka 2.5

Resultado igual o menor a echar una moneda al aire :). Necesitamos reinvindicar esto. Lean con mas cuidado el articulo y lo discutimos en algun momento.

RNAi que activa?

Por favor lean el siguiente articulo>

Nature 448, 855-858 (23 August 2007) | doi:10.1038/448855a; Published online 22 August 2007

RNA interference: Hitting the on switch

Estos dos investigadores han descubierto que RNAi dirigido a un promotor activa en vez de inhibir el gen. Esto es muy controversial y vale la pena leer este articulito para que vean lo que han sufrido estos dos investigadores con su linea (y como les han rechazado varios articulos en nature, a pesar de que ahora pongan un articulo de como les ha ido)
No olviden el ejercicio que les deje en el post pasado!!!

Celulas stem

Este es un articulo muy interesante

Is Bacterial Persistence a Social Trait?

Andy Gardner^1,2*, Stuart A. West², Ashleigh S. Griffin²

1 St John's College, Oxford University, Oxford, United Kingdom, 2 Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom

The ability of bacteria to evolve resistance to antibiotics has been much reported in recent years. It is less well-known that within populations of bacteria there are cells which are resistant due to a non-inherited phenotypic switch to a slow-growing state. Although such ‘persister’ cells are receiving increasing attention, the evolutionary forces involved have been relatively ignored. Persistence has a direct benefit to cells because it allows survival during catastrophes–a form of bet-hedging. However, persistence can also provide an indirect benefit to other individuals, because the reduced growth rate can reduce competition for limiting resources. This raises the possibility that persistence is a social trait, which can be influenced by kin selection. We develop a theoretical model to investigate the social consequences of persistence. We predict that selection for persistence is increased when: (a) cells are related (e.g. a single, clonal lineage); and (b) resources are scarce. Our model allows us to predict how the level of persistence should vary with time, across populations, in response to intervention strategies and the level of competition. More generally, our results clarify the links between persistence and other bet-hedging or social behaviours.

Esto lleva a un blog a postular un posible parecido con las celulas stem, lo cual es muy interesante para el caso del cancer. Seria posible que las celulas stem cancerosas puedan tener este comportamiento? Es decir comportarse como stem por razones fenotipicas y no genotipicas y cambiar de un estado a otro. Esto explicaria el articulo de k. polyak que difiere de la mayoria y podria dar una teoria que cubriera todo.

Que se les ocurre hacer para comprobar esta hipotesis? Me gustaria que todos intentaran contestar (en comentarios). Es mas, lo hacemos obligatorio como un ejercicio. No se preocupen de poner algo que consideren tonto, solo asi se aprende.

Mutaciones en NF-kappa B

Es muy conocido que NF-kappa B se encuentra activado en practicamente todos los tumores. Sin embargo, la razon especifica para esta activacion no ha sido aclarada para cada tipo tumoral. Dos nuevos articulos en Cancer Cell (August 2007, 12(2)) reportan que alrededor del 20% de los mielomas multiples presentan mutaciones en diversos componentes de la cascada canonica o no canonica, incluyendo mutaciones con perdida de funcion en reguladores negativos como TRAF2, TRAF3, IAP1 y 2 y CYLD como mutaciones activantes en genes positivos como amplificacion de NIK, NFkB1 (p50/105) NFkB2 (p52/100), CD40, LTBR, etc.
Es mas, al inhibir la activacion de NFkB en lineas con estas alteraciones se induce apoptosis. Adicionalmente, uno de los articulos valida el uso de microarreglos de expresion para identificar mutaciones, algo mucho mas facil que aproximaciones genomicas (CGH, etc).

Avance cientifico. Teoria del Cha-cha-cha

Filosofia de la ciencia.
Este articulo en el ultimo numero de Science (Science 10 August 2007: Vol. 317. no. 5839, pp. 761 - 762) es interesante. Es un homenaje al recientemente fallecido ex-editor de Science, en el que categoriza el avance cientifico en tres tipos:

""Charge" discoveries solve problems that are quite obvious--cure heart disease, understand the movement of stars in the sky--but in which the way to solve the problem is not so clear. In these, the scientist is called on, as Nobel laureate Albert Szent-Györgyi put it, "to see what everyone else has seen and think what no one else has thought before." Thus, the movement of stars in the sky and the fall of an apple from a tree were apparent to everyone, but Isaac Newton came up with the concept of gravity to explain it all in one great theory.

"Challenge" discoveries are a response to an accumulation of facts or concepts that are unexplained by or incongruous with scientific theories of the time. The discoverer perceives that a new concept or a new theory is required to pull all the phenomena into one coherent whole. Sometimes the discoverer sees the anomalies and also provides the solution. Sometimes many people perceive the anomalies, but they wait for the discoverer to provide a new concept. Those individuals, whom we might call "uncoverers," contribute greatly to science, but it is the individual who proposes the idea explaining all of the anomalies who deserves to be called a discoverer.

"Chance" discoveries are those that are often called serendipitous and which Louis Pasteur felt favored "the prepared mind." In this category are the instances of a chance event that the ready mind recognizes as important and then explains to other scientists. This category not only would include Pasteur's discovery of optical activity (D and L isomers), but also W. C. Roentgen's x-rays and Roy Plunkett's Teflon. These scientists saw what no one else had seen or reported and were able to realize its importance."

CATEGORIES OF DISCOVERY
Problem that needed solving	Discovery	Discoverer	Category of discovery
Movement of stars, Earth, and Sun	Gravity	Newton	Charge
Structure of C6H6	Benzene structure	Kekulé	Challenge
Clear spots on petri dish	Penicillin	Fleming	Chance
Constant speed of light	Special relativity	Einstein	Challenge
Preventing heart attacks	Cholesterol metabolism	Brown & Goldstein	Charge
Crystals of D- and -L tartaric acid	Optical activity	Pasteur	Chance
Atomic spectra that could not be explained	Quantum mechanical atom	Bohr	Challenge
How DNA replicates and passes on coding	Base pairing in double helix	Watson & Crick	Challenge
Reagent "stuck" in storage cylinder	Teflon	Plunkett	Chance
Why offspring look like their parents	Laws of heredity	Mendel	Charge

Smac/DIABLO se fosforila

Phosphorylation of Smac by JNK3 attenuates its interaction with XIAP.

Biochem Biophys Res Commun. 2007 Jul 31;

Authors: Park BD, Ham YM, Jeong HJ, Cho SJ, Je YT, Yoo KD, Lee SK

Here we demonstrate that JNK3 can phosphorylate Smac. Smac phosphorylation attenuates its ability to activate apoptosome activity in HeLa S-100 cell lysates. Addition of the X-linked inhibitor of apoptosis protein (XIAP) to the S-100 markedly suppresses apoptosome activity, and this suppressive effect of XIAP is neutralized by adding unphosphorylated Smac, but not phosphorylated Smac. Furtherover, JNK3-mediated phosphorylation of Smac markedly attenuates the interaction between Smac and XIAP, as measured by BIACORE assays and non-denaturing gel shift assays. When JNK3 activity is down-regulated in etoposide-induced HeLa cells by transiently overexpressing a dominant negative version of JNK3 (DN-JNK3), the caspase-3 activity as well as PARP cleavages are markedly enhanced. And the interaction of Smac with XIAP also increases by down-regulating JNK3 activity under the same conditions. These results suggest that JNK3 activity can attenuate the progression of apoptosis through a novel mechanism of action, the down-regulation of interaction between Smac and XIAP

p53. Efectos supresores independientes de apoptosis?

Una hipotesis muy arraigada es que la capacidad de p53 para suprimir tumores de p53 esta mediada por su habilidad para inducir apoptosis en celulas que tienen su ADN dañado. Este nuevo articulo contribuye a la idea de que esto no es universal, y que pueden existir tumores especificos en donde p53 suprime por otro mecanismo:

Nature Medicine 13, 992 - 997 (2007)
David G Kirsch

A spatially and temporally restricted mouse model of soft tissue sarcoma

Soft tissue sarcomas are mesenchymal tumors that are fatal in approximately one-third of patients. To explore mechanisms of sarcoma pathogenesis, we have generated a mouse model of soft tissue sarcoma. Intramuscular delivery of an adenovirus expressing Cre recombinase in mice with conditional mutations in Kras and Trp53 was sufficient to initiate high-grade sarcomas with myofibroblastic differentiation. Like human sarcomas, these tumors show a predilection for lung rather than lymph node metastasis. Using this model, we showed that a prototype handheld imaging device can identify residual tumor during intraoperative molecular imaging. Deletion of the Ink4a-Arf locus (Cdkn2a), but not Bak1 and Bax, could substitute for mutation of Trp53 in this model. Deletion of Bak1 and Bax, however, was able to substitute for mutation of Trp53 in the development of sinonasal adenocarcinoma. Therefore, the intrinsic pathway of apoptosis seems sufficient to mediate p53 tumor suppression in an epithelial cancer, but not in this model of soft tissue sarcoma.
Por ende, p53 emplea otro mecanismo de supresion en el caso de estos sarcomas

Nuevo papel de p53

El gen supresor p53, conocido como "el guardián del genoma", tiene un papel fundamental en la respuesta al daño al ADN (como el producido por las drogas antineoplásicas), al activar ya sea el proceso de arresto celular, si el daño es reparable, o apoptosis, si no lo es. Más del 50% de los tumores tienen mutado o perdido este gen, lo que resalta su importancia. Acaban de describir una nueva función de p53, como un inhibidor de la migración, lo que tiene mucho sentido para la fisiopatología del cáncer.

p53 and RhoA signalling: A round about way for tumour invasion

Cell Migration Gateway (August 2007) | doi:10.1038/cmg051

Knocking out the tumour suppressor p53 causes cells to shift from an elongated to a rounded morphology, which is associated with increased motility and tumour invasiveness.

"The role of p53 in controlling cell-cycle arrest and apoptosis has been well-characterised but the tumour suppressor has more recently been linked with cell morphology. Published in The Journal of Cell Biology, Roux and colleagues report that p53 affects cell migration morphology by controlling localisation of the key cytoskeletal regulator RhoA, leading to an increase in cell invasiveness."

".....Thus, p53 modulates cell migration by controlling RhoA localization and regulating the RhoA-ROCK signalling pathway. Loss of p53 results in the aberrant overactivation of RhoA and ROCK-dependent translocation of RhoA to membrane blebbing structures."

Problemas en la lectura de MTT

Los ensayos de citotoxicidad que hacemos involucran varias tecnicas, entre ellas la del MTT. Este articulo señala que el suero fetal bovino, por la cantidad de albumina, podria dar problemas en la lectura.
BioTechniques® August 2007
Volume 43, Number 2: pp 178-186
Serum albumin leads to false-positive results in the XTT and the MTT assay
Dorothee Funk, Hans-Hermann Schrenk, and Eva Frei

Abstract
Tetrazolium salts like 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) or sodium 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H- tetrazolium-5-carboxanilide (XTT) that form formazans after reduction are widely used to investigate cell viability. Besides cellular enzymes, some constituents of cell media and other substances reduce tetrazolium salts, thereby interfering with these assays. We describe here that different preparations of serum albumin from bovine or human origin can lead to a concentration-dependent increase in the signals of the XTT assay; therefore leading to an overestimation of cell numbers and to an underestimation of potential cytotoxic effects of compounds to be tested. The same effect was seen in the MTT assay with human serum albumin (HSA). We demonstrate that this reductive activity cannot be inactivated by proteolytic digestion, but that it is due to the free cysteine residue in albumin, and is also observed when cysteine or glutathione (GSH) are used. Binding of N-ethylmaleimide (NEM) to the free cysteine residue leads to a decrease of the albumin interference in the XTT assay.

"...reduced XTT and MTT to the corresponding formazan and might explain the observation of Zhang and Cox who observed a 20% higher formazan signal when cells were assayed in 10% fetal calf serum (FCS) rather than in 5% FCS (16).Based on these findings, we strongly recommend to be careful with data from XTT and MTT assays when estimating cytotoxicity when albumin or other proteins with free SH groups are present, because the artificial increase in the assay signal, which is not due to cellular reductases, could lead to an underestimation of the cytotoxicity of the compounds to be tested"