abstract：:Innate immunity is the first line of defense against invading pathogens. A family of Toll-like receptors (TLRs) acts as primary sensors that detect a wide variety of microbial components and elicit innate immune responses. All TLR signaling pathways culminate in activation of the transcription factor nuclear factor-ka...

journal_title：Trends in molecular medicine

authors： Kawai T,Akira S

更新日期：2007-11-01 00:00:00

abstract：:Environmental effects on the materno-foetal interaction determine birth outcomes that predict health over the lifespan. Thus, maternal undernutrition or stress associate with low birth weight, leading to an increased risk of metabolic and cardiovascular illness in the offspring. We argue that these effects are, in par...

journal_title：Trends in molecular medicine

authors： Meaney MJ,Szyf M,Seckl JR

更新日期：2007-07-01 00:00:00

abstract：:Recurrent pregnancy loss (RPL), which occurs in 0.5%-1% of total pregnancies, is usually defined as three or more consecutive spontaneous abortions before 20 weeks of gestation. Although an immunology-based etiology underlying unexplained RPL has been demonstrated, the exact molecular mechanisms are still poorly under...

journal_title：Trends in molecular medicine

authors： Baek KH,Lee EJ,Kim YS

更新日期：2007-07-01 00:00:00

abstract：:Migraine is a complex, disabling disorder of the brain that manifests itself as attacks of often severe, throbbing head pain with sensory sensitivity to light, sound and head movement. There is a clear familial tendency to migraine, which has been well defined in a rare autosomal dominant form of familial hemiplegic m...

journal_title：Trends in molecular medicine

authors： Goadsby PJ

更新日期：2007-01-01 00:00:00

abstract：:Transport into the endoplasmic reticulum (ER) is the crucial step in the biosynthesis of most secretory proteins and many membrane proteins. The products of the SIL1, SEC62 and SEC63 genes act in concert with the SEC61 complex and the molecular chaperones BiP and GRP170 to transport proteins into the ER. Interestingly...

journal_title：Trends in molecular medicine

authors： Zimmermann R,Müller L,Wullich B

更新日期：2006-12-01 00:00:00

abstract：:The vanilloid receptor TRPV1 is now recognized as a molecular integrator of painful stimuli ranging from noxious heat to endovanilloids in inflammation. Pharmacological blockade of TRPV1 represents a new strategy in pain relief. TRPV1 antagonists are expected to prevent pain by silencing receptors where pain is genera...

journal_title：Trends in molecular medicine

authors： Szallasi A,Cruz F,Geppetti P

更新日期：2006-11-01 00:00:00

abstract：:To prevent duplication or loss of genomic regions during DNA replication, it is essential that the entire genome is copied precisely once every S phase. Cells achieve this by mutually exclusive regulation of origin firing and licensing. A crucial protein that is involved in origin licensing is chromatin licensing and ...

journal_title：Trends in molecular medicine

authors： Green CM

更新日期：2006-10-01 00:00:00

abstract：:The social amoeba Dictyostelium discoideum is increasingly being used as a simple model for the investigation of problems that are relevant to human health. This article focuses on several recent examples of Dictyostelium-based biomedical research, including the analysis of immune-cell disease and chemotaxis, centroso...

journal_title：Trends in molecular medicine

authors： Williams RS,Boeckeler K,Gräf R,Müller-Taubenberger A,Li Z,Isberg RR,Wessels D,Soll DR,Alexander H,Alexander S

更新日期：2006-09-01 00:00:00

abstract：:Carbon monoxide, long considered only as a toxic gas, has recently been shown to mediate potent anti-inflammatory and other salutary effects in rodents when it is used at low doses. Carbon monoxide is one of the products of the degradation of heme by heme oxygenase 1. Until recently, these beneficial effects of carbon...

journal_title：Trends in molecular medicine

authors： Bach FH

更新日期：2006-08-01 00:00:00

abstract：:Adult skeletal muscle has remarkable regenerative potential, which is mainly attributable to a small population of undifferentiated skeletal muscle precursors called satellite cells. These cells reside underneath the basal lamina of skeletal myofibers and can be activated to proliferate, differentiate and fuse to form...

journal_title：Trends in molecular medicine

authors： Sherwood RI,Wagers AJ

更新日期：2006-05-01 00:00:00

abstract：:The placenta is central to foetal growth and development in mammalian pregnancy. Compromised placental function (as found in pre-eclampsia) often results in life-threatening situations for both mother and foetus. The nitric-oxide (NO) signalling cascade is important for placental function, in particular for the develo...

journal_title：Trends in molecular medicine

authors： Vatish M,Randeva HS,Grammatopoulos DK

更新日期：2006-05-01 00:00:00

abstract：:T-cell-mediated autoimmunity participates in physiological defense, maintenance and repair of the adult brain. However, unless such autoimmune responses to insults are rigorously controlled, they might lead to an autoimmune disease or other immune-related defects, where destructive activity outweighs the beneficial ef...

journal_title：Trends in molecular medicine

authors： Kipnis J,Cardon M,Strous RD,Schwartz M

更新日期：2006-03-01 00:00:00

abstract：:Degenerated motor neurons in the spinal cord are the pathological hallmark of spinal muscular atrophy (SMA). SMA is caused by mutations in the ubiquitously expressed survival motor neuron 1 (SMN1) gene, which lead to reduced levels of functional SMN protein. Many different functions have been assigned to SMN, includin...

journal_title：Trends in molecular medicine

authors： Eggert C,Chari A,Laggerbauer B,Fischer U

更新日期：2006-03-01 00:00:00

abstract：:The past few years have seen the identification of PTPN22 and the confirmation of CTLA-4 as common autoimmune disease genes. Together with MHC and INS, these developments have increased the collection of confirmed susceptibility loci for autoimmunity. In this article, the latest developments related to these genes and...

journal_title：Trends in molecular medicine

authors： Pearce SH,Merriman TR

更新日期：2006-02-01 00:00:00

abstract：:Hundreds of millions of people worldwide are affected by bone-related diseases, such as osteoporosis and rheumatoid arthritis. Understanding the molecular mechanisms of bone metabolism is crucial for developing novel drugs for treating such diseases. In particular, genetic experiments showing that the receptor activat...

journal_title：Trends in molecular medicine

authors： Wada T,Nakashima T,Hiroshi N,Penninger JM

更新日期：2006-01-01 00:00:00

abstract：:There is already considerable evidence from epidemiological, pathological and clinical reports that vascular factors are crucial in the pathogenesis of Alzheimer's disease (AD). Cerebral hypoperfusion has been shown to be a preclinical condition and a most accurate indicator for predicting whether people will develop ...

journal_title：Trends in molecular medicine

authors： de la Torre JC

更新日期：2005-12-01 00:00:00

abstract：:H(2)O(2) is a reactive oxygen species that has drawn much interest because of its role as a second messenger in receptor-mediated signaling. Mammalian 2-Cys peroxiredoxins have been shown to eliminate efficiently the H(2)O(2) generated in response to receptor stimulation. 2-Cys peroxiredoxins are members of a novel pe...

journal_title：Trends in molecular medicine

authors： Kang SW,Rhee SG,Chang TS,Jeong W,Choi MH

更新日期：2005-12-01 00:00:00

abstract：:Medulloblastomas often activate Hedgehog signaling inappropriately. The finding that mutations in components of this pathway are present only in few tumors suggests that additional genetic or epigenetic lesions can also lead to Hedgehog dysregulation. Chromosome 17p deletion, the most frequently detected genetic lesio...

journal_title：Trends in molecular medicine

authors： Ferretti E,De Smaele E,Di Marcotullio L,Screpanti I,Gulino A

更新日期：2005-12-01 00:00:00

abstract：:Ubiquitin-containing cellular inclusions are characteristic of major neurodegenerative diseases and suggest an involvement of the ubiquitin-proteasome system. The frameshifted form of ubiquitin has proved to be a valuable tool for studying the role of the ubiquitin-proteasome system. It is an endogenous reporter for p...

journal_title：Trends in molecular medicine

authors： Hol EM,van Leeuwen FW,Fischer DF

更新日期：2005-11-01 00:00:00

abstract：:Prion diseases are infectious neurodegenerative fatal disorders. There are currently no treatments or cures. Considerable evidence suggests that the infectious agent is an abnormally folded protein that promotes or seeds its normal cellular isoform to fold into the infectious form. However, the precise mechanism and f...

journal_title：Trends in molecular medicine

authors： Liebman SW,Mastrianni JA

更新日期：2005-10-01 00:00:00

abstract：:Many infectious agents elicit a type I interferon response but, until recently, the molecular details that coordinate interferon (IFN)-alpha and -beta expression during infection were unknown. Innate immune pattern recognition receptors, including Toll-like receptors and cytoplasmic RNA helicases such as retinoic acid...

journal_title：Trends in molecular medicine

authors： Jefferies CA,Fitzgerald KA

更新日期：2005-09-01 00:00:00

abstract：:The deregulation of tyrosine kinase receptors (RTKs) is frequent in human tumors and is often associated with the acquisition of an aggressive phenotype. The Met oncogene, encoding the RTK for hepatocyte growth factor (HGF), controls genetic programs leading to cell growth, invasion and protection from apoptosis. The ...

journal_title：Trends in molecular medicine

authors： Corso S,Comoglio PM,Giordano S

更新日期：2005-06-01 00:00:00

abstract：:For decades it has been assumed that T cells reject tumors essentially by direct killing. However, solid tumors are composed of malignant cells and a variety of different nonmalignant cells, referred to as tumor stroma. Stromal cells, such as endothelial cells, fibroblasts and inflammatory cells, often support tumor g...

journal_title：Trends in molecular medicine

authors： Kammertoens T,Schüler T,Blankenstein T

更新日期：2005-05-01 00:00:00

abstract：:BRCA2 was identified in 1995, one year after BRCA1. In terms of knowledge of the function of its product, BRCA2 has remained the less well-characterised gene. Both BRCA1 and BRCA2 are closely implicated in the repair of double-strand breaks in DNA by homologous recombination, but beyond that a function for BRCA2 has b...

journal_title：Trends in molecular medicine

authors： Rudkin TM,Foulkes WD

更新日期：2005-04-01 00:00:00

abstract：:cAMP-dependent protein kinase A (PKA) signaling has a key role in memory processes and has been identified as a potential therapeutic target for memory disorders. The activation of PKA signaling is crucial for the consolidation of long-term memories dependent on the hippocampus and/or the amygdala, By contrast, initia...

journal_title：Trends in molecular medicine

authors： Arnsten AF,Ramos BP,Birnbaum SG,Taylor JR

更新日期：2005-03-01 00:00:00

abstract：:The cells of bone and the immune system communicate by means of soluble and membrane-bound cytokines and growth factors. Through local signalling mechanisms, cells of the osteoblast lineage control the formation and activity of osteoclasts and, therefore, the resorption of bone. Both T and B lymphocytes produce activa...

journal_title：Trends in molecular medicine

authors： Martin TJ,Sims NA

更新日期：2005-02-01 00:00:00

abstract：:Betulinic acid (BA) derivatives are low molecular weight organic compounds synthesized from a plant-derived natural product. Several BA derivatives are potent and highly selective inhibitors of HIV-1. Depending on the specific side-chain modification, these compounds function by inhibiting HIV fusion or, as recently d...

journal_title：Trends in molecular medicine

authors： Aiken C,Chen CH

更新日期：2005-01-01 00:00:00

abstract：:Pyocyanin (PCN) is a blue redox-active secondary metabolite that is produced by Pseudomonas aeruginosa. PCN is readily recovered in large quantities in sputum from patients with cystic fibrosis who are infected by P. aeruginosa. Despite in vitro studies demonstrating that PCN interferes with multiple cellular function...

journal_title：Trends in molecular medicine

authors： Lau GW,Hassett DJ,Ran H,Kong F

更新日期：2004-12-01 00:00:00

abstract：:Long-standing difficulties in the in vitro transformation of human cells have been overcome. Using telomerase, several successful oncogene-mediated transformations of human cells have been reported and the following cellular requirements for human cell transformation have been proposed: the maintenance of telomere seq...

journal_title：Trends in molecular medicine

authors： Akagi T

更新日期：2004-11-01 00:00:00

abstract：:Rearrangements of the MLL gene, which is located at chromosome 11q23, are associated with aggressive acute leukemias in both children and adults. MLL regulates Hox gene expression through direct promoter binding and histone modification. MLL rearrangements occurring in leukemia include MLL fusion genes, partial tandem...

journal_title：Trends in molecular medicine

authors： Hess JL

更新日期：2004-10-01 00:00:00

abstract：:Ten years ago, the linkage between mutations in the gene coding for the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) and the neurodegenerative disease known as familial amyotrophic lateral sclerosis (FALS) was established. This finding has prompted a myriad of new studies in experimental models aimed at invest...

journal_title：Trends in molecular medicine

authors： Bendotti C,Carrì MT

更新日期：2004-08-01 00:00:00

abstract：:Nitric-oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs), which consist of an NSAID with an NO-donating moiety covalently attached to it, promise to contribute significantly towards the development of effective chemoprevention strategies against cancer. NO-NSAIDs inhibit the growth of cultured cancer cel...

journal_title：Trends in molecular medicine

authors： Rigas B,Kashfi K

更新日期：2004-07-01 00:00:00

abstract：:Serotonin is an important neurohormonal factor that has been implicated in cardiovascular function. It can regulate vascular tone, act directly on cardiomyocytes and stimulate chemosensitive nerves in the heart. Cardiovascular dysfunction is observed when serotonin signaling is altered or when variation in serotonin c...

journal_title：Trends in molecular medicine

authors： Côté F,Fligny C,Fromes Y,Mallet J,Vodjdani G

更新日期：2004-05-01 00:00:00

abstract：:Physicians have, for over a century, attempted to harness the potential therapeutic power of the immune system to treat patients with cancer. The discovery that cancer regression can be achieved by immune rejection of tumour antigens theoretically allows the eradication of neoplastic cells without toxicity to normal t...

journal_title：Trends in molecular medicine

authors： Stebbing J,Bower M,Srivastava P

更新日期：2004-04-01 00:00:00

abstract：:One hypothesis for the etiology of neuropsychiatric disorders proposes that viral infection contributes to the induction of neuronal system dysfunction, resulting in a wide range of behavioral abnormalities. Recent research in molecular biology supports this hypothesis and refocuses on the role of viral infection in t...

journal_title：Trends in molecular medicine

authors： Tomonaga K

更新日期：2004-02-01 00:00:00

abstract：:Transcription factor nuclear factor-kappaB (NF-kappaB) and its target genes are involved in the pathogenesis of atherosclerosis, in addition to many other diseases. Monocyte recruitment into subendothelial space is primarily mediated by NF-kappaB-dependent gene expression, and this event is a crucial milestone, becaus...

journal_title：Trends in molecular medicine

authors： Kutuk O,Basaga H

更新日期：2003-12-01 00:00:00

abstract：:Mutations in whirlin, a putative PDZ scaffold protein, have recently been shown to cause deafness and short cochlear hair cell stereocilia in whirler mice and recessive deafness (DFNB31) in humans. Through its PDZ domains, whirlin might organize a group of proteins into a functional complex required for stereocilia el...

journal_title：Trends in molecular medicine

authors： Belyantseva IA,Labay V,Boger ET,Griffith AJ,Friedman TB

更新日期：2003-11-01 00:00:00

abstract：:The identification of functionally relevant polymorphisms of peptidylarginine deiminase 4, an enzyme that catalyzes the post-translational citrullination of proteins, as a rheumatoid arthritis gene is one of the most convincing success stories of complex disease gene mapping to date. In addition to an extensive single...

journal_title：Trends in molecular medicine

authors： Worthington J,John S

更新日期：2003-10-01 00:00:00

abstract：:Autosomal dominant polycystic kidney disease (ADPKD) is a common lethal genetic disorder, characterized by the progressive development of fluid-filled cysts in the kidney, pancreas and liver, and anomalies of the cardiovascular system. Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 (P...

journal_title：Trends in molecular medicine

authors： Cantiello HF

更新日期：2003-06-01 00:00:00

abstract：:Post-transcriptional RNA editing generates novel gene products by changing the coding sequence of the transcript from that in the genome. Two classes of RNA editing exist in mammals, each of which involves an enzymatic deamination. These reactions have stringent sequence and structural requirements for their target RN...

journal_title：Trends in molecular medicine

authors： Anant S,Davidson NO

更新日期：2003-04-01 00:00:00