Abstract:
:Seen from the perspective of funding organizations, investors, and the general public, the productivity of our world-wide biomedical research enterprise is declining despite increased investment. This opinion piece suggests a cause and a solution. The cause is the enormous complexity of human biology and pathophysiology. The unsolved human diseases involve so many interacting variables that single research laboratories headed by skilled principal investigators doing innovative experimental work cannot be expected to assemble the reductionist pieces into an integrated working model. Systems biology offers a solution, but it will require teamwork. Co-equal teams of experimental and computational biologists can construct multiscale differential equation models and test them against experimental data. A successful model provides actionable evidence-based guidance to the entire research and development team. These integrative biology teams may, for historical and cultural reasons, be unsustainable in academia, but they seem naturally suited to modern pharmaceutical research and development. One way to organize such teams and their workflow is described in detail.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Phair RDdoi
10.1007/978-1-4419-7210-1_31subject
Has Abstractpub_date
2012-01-01 00:00:00pages
533-42eissn
0065-2598issn
2214-8019journal_volume
736pub_type
杂志文章abstract::Matrix assisted laser desorption ionization (MALDI) mass spectrometry allows for the rapid profiling of different biomolecular species from both biofluids and tissues. Whilst originally focused upon the analysis of intact proteins and peptides, MALDI mass spectrometry has found further applications in lipidomic analys...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-030-15950-4_2
更新日期:2019-01-01 00:00:00
abstract::A common characteristic among fungal pathogens of plants is that each specializes on a narrow range of specific plants as hosts. One adaptation to a specific host plant is the recognition of the host's chemicals which can be used to trigger genes or developmental pathways needed for pathogenesis. The production of cha...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4757-5235-9_2
更新日期:2002-01-01 00:00:00
abstract::Recent progress in tissue-resident adult stem/progenitor cell research has inspired great interest because these immature cells from your own body can act as potential, easily accessible cell sources for cell transplantation in regenerative medicine and cancer therapies. The use of adult stem/progenitor cells endowed ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-2098-9_12
更新日期:2012-01-01 00:00:00
abstract::The adverse effects of trace metals, heat, steam and other conditions encountered in food processing relate to the acceleration of development of rancidity. Measures to retard oxidation of lipids, vitamins, pigments and proteins include elimination of prooxidants, removal of oxygen and use of blends of inhibitors form...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4899-1925-0_16
更新日期:1998-01-01 00:00:00
abstract::To investigate whether altered renal medullary prostaglandin (PG) synthesis is involved in the development of hypertension in spontaneously hypertensive rats (SHR), we compared the capacity of PGE2 synthesis in cultured renal papillary collecting tubule cells from young (4-week-old) and aged (16-week-old) SHR and cont...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-9546-5_83
更新日期:1989-01-01 00:00:00
abstract::The revised sequence of DaaA means that the protein is 98% identical to the afimbrial adhesin regulator AFAA-III. While PapB repressed FimB OFF to ON switching in strain AAEC370A, this was not the case for DaaA. PapB, but not DaaA, reduced the level of expression of type 1 fimbriae, in static LB media. Attention is no...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/0-306-46840-9_20
更新日期:2000-01-01 00:00:00
abstract::Lung diseases affect millions of individuals all over the world. Various environmental factors, such as toxins, chemical pollutants, detergents, viruses, bacteria, microbial dysbiosis, and allergens, contribute to the development of respiratory disorders. Exposure to these factors activates stress responses in host ce...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-030-45328-2_4
更新日期:2020-01-01 00:00:00
abstract::Diabetes mellitus (DM) is a metabolic disorder characterised by hyperglycemia and abnormalities in carbohydrate, fat and protein metabolism. Several studies demonstrated that foods typical of the Mediterranean diet (MedDiet), including vegetables, fruits, oilseeds, extra virgin olive oil and fish, can promote health b...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/5584_2020_513
更新日期:2021-01-01 00:00:00
abstract::Ascidians possess relatively small and compact genomes. This feature enables us to easily isolate cis-regulatory DNAs of genes of interest. Particularly, cis-regulatory DNAs of genes showing tissue- or cell-type-specific expression are routinely used for the artificial induction of gene expression. This strategy helps...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-10-7545-2_6
更新日期:2018-01-01 00:00:00
abstract::The first purpose of this work was to obtain direct evidence that tissue kallikreins cleave arginyl bonds when the leaving group is Arg-Val, and on the contrary, do not split them when it is Arg-Pro; the second aim was to ascertain whether this specificity could be used as a criterion, for characterizing tissue kallik...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-5143-6_33
更新日期:1986-01-01 00:00:00
abstract::This review covers recent advances in a variety of dyskinesias. Introduction of new drugs for the treatment of myoclonus and sensory biofeedback therapy for focal dystonia are expanding our concepts of these types of movement disorders. Progress in the treatment of action myoclonus is especially noteworthy and has led...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-2511-6_7
更新日期:1977-01-01 00:00:00
abstract::Prevalence of zoonotic Mycobacterium bovis (bTB) disease in human population is underreported from the North of Pakistan. Here, we report on the proportion of human bTB disease among the overall TB patients, drug resistance pattern of bTB isolates, and knowledge, attitude, and practices (KAP)-based analysis of bTB dis...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/5584_2018_170
更新日期:2018-01-01 00:00:00
abstract::Despite the lack of adaptive immunity based on gene rearrangement such as that in higher vertebrates, flies are able to defend themselves from a wide array of pathogens using multiple innate immune responses whose molecular mechanisms are strikingly similar to those of the innate immune responses of other multicellula...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4419-8059-5_11
更新日期:2010-01-01 00:00:00
abstract::The CD1 system is composed of five types of human CD1 proteins, CD1a, CD1b, CD1c, CD1d, and CD1e, and their mammalian orthologs. Each type of CD1 protein has a distinct antigen binding groove and shows differing patterns of expression within cells and in different tissues. Here we review the molecular mechanisms by wh...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-6111-1_10
更新日期:2013-01-01 00:00:00
abstract::Taurine is traditionally used to treat Down Syndrome (DS); however, the actual foundation for this treatment is not well understood. DS patients suffer from disturbance of the proteostasis network (PN) due to aberrant calcium signaling, which eventually causes endoplasmic reticulum stress (ERS). Taurine has been sugge...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-981-13-8023-5_40
更新日期:2019-01-01 00:00:00
abstract::The analysis of different Wavelets including novel Wavelet families based on atomic functions are presented, especially for ultrasound (US) and mammography (MG) images compression. This way we are able to determine with what type of filters Wavelet works better in compression of such images. Key properties: Frequency ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4419-7046-6_50
更新日期:2011-01-01 00:00:00
abstract::Diseases can be caused naturally by biological agents such as bacteria, viruses and toxins (natural risk). However, such biological agents can be intentionally disseminated in the environment by a State (military context) or terrorists to cause diseases in a population or livestock, to destabilize a nation by creating...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-72077-7_9
更新日期:2017-01-01 00:00:00
abstract::The discovery that PSD-95/Discs large/ZO-1 (PDZ) domains can function as lipid-binding modules, in particular interacting with phosphoinositides (PIs), was made more than 10 years ago (Mol Cell 9(6): 1215-1225, 2002). Confirmatory studies and a series of functional follow-ups established PDZ domains as dual specificit...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-94-007-6331-9_4
更新日期:2013-01-01 00:00:00
abstract::The incidence and severity of retinopathy of prematurity (ROP) were studied in 561 survivors of low birth weight infants (LBWIs) weighing under 2,000g. They were the survivors out of 604 LBWIs admitted to Okayama National Hospital during the five years from January 1981 to December 1985. The tcPO2 of all the LBWIs on ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4613-1927-6_19
更新日期:1987-01-01 00:00:00
abstract::Adenomatous Polyposis Coli (APC) is a tumor suppressor protein involved in the initiation and progression of colon cancer. The most widely accepted function ofAPC is to participate to the Wnt signaling pathway, by downregulating beta-catenin and thereby controlling gene transcription and cell proliferation. However, A...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4419-1145-2_3
更新日期:2009-01-01 00:00:00
abstract::Blood flow of human mammary carcinomas heterotransplanted into immune- deficient rnu/rnu-rats is low. It decreases further with increasing tumor wet weight, the mean value being comparable to that of mammary carcinomas in patients. The O2 consumption rate of the heterotransplanted tumors decreases with increasing tumo...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-3291-6_76
更新日期:1985-01-01 00:00:00
abstract::Modern society is witnessing a widespread tendency to postpone parenthood due to a number of socioeconomic factors. This ever-increasing trend relates to both women and men and raises many concerns about the risks and consequences lying beneath the natural process of aging. The negative influence of the advanced mater...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-7783-9_2
更新日期:2014-01-01 00:00:00
abstract::Single frog skeletal muscle fibres were stretched during fused tetanic contractions. The force increase during stretch exhibited a breakpoint at a mean critical length change of 16.6 nm per half sarcomere that was independent of stretch velocity and sarcomere length. The early decaying extra force after stretch (compo...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-4703-3_71
更新日期:1984-01-01 00:00:00
abstract::During gamma-irradiation (5 kGy) of aqueous tryptophan (Trp) solutions small amounts of 5-, 6-, and 7-hydroxytryptophan (OH-Trp) (0.04-0.08 Mol-%) are formed. Protein rich food like shrimps contain reasonable amounts of non-protein bound Trp (100 mg/kg). In order to detect the treatment of shrimps with gamma-irradiati...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-0135-0_80
更新日期:2003-01-01 00:00:00
abstract::The sarcomere stiffness was measured in single muscle fibres during the development of tetanic tension using a method insensitive to fibre inertia and viscosity. The stiffness was calculated as the ratio between tension changes and sarcomere length changes during a period of fast sarcomere elongation at constant veloc...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-6039-1_43
更新日期:1998-01-01 00:00:00
abstract::Though soft tissue disorders have been recognized and described to some detail in several types of domestic animals and small mammals for some years, not much progress has been made in our understanding of the biochemical basis and pathogenesis of these diseases in animals. Ehlers-Danlos syndrome described in dogs alr...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-94-007-7893-1_14
更新日期:2014-01-01 00:00:00
abstract::Vitamin A is metabolized to several biologically active compounds, the best known of which is retinoic acid. This compound has been shown to inhibit the growth of a variety of tumor cells and to induce a more differentiated phenotype in several tumor types. Vitamin D is metabolized to the active compound 1,25-dihydrox...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4899-0949-7_1
更新日期:1995-01-01 00:00:00
abstract::Lymphoid and leukemic cells are uniquely sensitive to the lytic actions of glucocorticoid hormones which activate a programmed cell death in these cells. The response to glucocorticoids is sensitive to modulations at each step of hormone action: cellular uptake, binding and activation of cytosolic receptors, nuclear t...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4615-4811-9_67
更新日期:1999-01-01 00:00:00
abstract::Signaling in tenocytes during development, homeostasis and injury involves multiple and redundant pathways. Given that tendons transmit mechanical forces from muscle to bone to effect movement, a key function for tenocytes is the detection of and response to mechanical stimulation. Mechanotransduction involves matrix-...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-33943-6_7
更新日期:2016-01-01 00:00:00
abstract::Notch signaling exerts multiple important functions in the hematopoietic system. Notch1-mediated signals are essential to induce the onset of definitive hematopoiesis within specialized domains of hemogenic endothelium in the fetal dorsal aorta. In contrast, Notch is dispensable for the subsequent maintenance of hemat...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-0899-4_6
更新日期:2012-01-01 00:00:00