The human c-ras1H oncogene: a mutation in normal and neoplastic tissue from the same patient

The c-ras1H oncogene can be distinguished from its normal cellular counterpart by the loss of a restriction endonuclease site. This sequence alteration is the basis of a rapid screening method for the presence of this oncogene. DNA's from 34 individuals were screened by this method, and all were homozygous for the normal allele. In contrast, DNA from a patient's bladder tumor, as well as DNA from his normal bladder and leukocytes, were heterozygous at that restriction endonuclease site. Further restriction enzyme mapping pinpointed the change in the mutant allele as being one of two nucleotides, either of which would change the 12th amino acid (glycine) in the normal c-ras1H gene product. Point mutations in the codon for this amino acid have previously been described in a bladder tumor cell line and in the viral oncogene v-rasH. These results indicate that the patient carried a c-ras1H oncogene in his germ line, raising the possibility that the c-ras1H oncogene confers a predisposition to neoplasia.     

Derivatives of erythropoietin that are tissue protective but not erythropoietic

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.     

Color defect and color theory; studies of normal and colorblind persons,including a subject color-blind in one eye but not in the other

It is important to find answers to two questions concerning the visual discriminations of dichromatic persons, especially deuteranopes: (i) Do such persons show a loss of sensitivity to various wavelengths of the spectrum as compared with normal subjects? (ii) What colors do they see? A number of experiments were performed on the first question. First, luminosity curves were determined on three groups of subjects, consisting respectively of five protanopes, six deuteranopes, and seven normal individuals. As compared with normal subjects, protanopes show a loss of luminosity in the red, whereas deuteranopes show a loss in the blue-to-green region of the spectrum (See 10). Second, we examined the luminosity curves of a subject whose right eye is classifiable (on the basis of color-mixture determinations) as normal and whose left eye is classifiable as dichromatic. (The hue discrimination curve for her dichromatic eye seemed comparable to the curve of the usual deuteranope except in the violet, where it manifested relatively good discrimination.) The luminosity function for this subject's dichromatic eye, determined by data on threshold and flicker, exhibits the same type of luminosity loss in the blue and green regions of the spectrum as was shown by our group of six deuteranopes. Only unilaterally dichromatic subjects can tell us how colors seen by a dichromatic eye appear to a normal eye. In the color-blind eye, our unilaterally dichromatic subject sees wavelengths below and above her neutral ("grey") point (which occurs at 502 mmicro) as, respectively, a blue equivalent to about 470 mmicro and a yellow equivalent to about 570 mmicro in her normal eye. The results on (i) luminosity loss and (ii) the seeing of wavelengths above 502 mmicro as yellow are considered theoretically. The seeing of yellow by deuteranopes and protanopes may be accounted for by an idea based on Leber-Fick transmation theory. It is proposed that the characteristic sensitivities of the red and green receptors become similar while no change takes place in their central brain connections. Losses may be introduced into the transformed sensitivity curves to indicate appropriate degrees of luminosity deficit for deuteranopes and protanopes.     

Detection of alpha-transducin in retinal rods but not cones

The distribution in chicken retina of the alpha subunit of transducin, the guanine nucleotide--binding protein that couples light-dependent activation of rhodopsin with activation of guanosine 3',5'-monophosphate phosphodiesterase, was determined with the aid of a specific antiserum. alpha-Transducin was found in rod photoreceptor cells but was not detected in cones. These results show that rods and cones differ with respect to alpha-transducin content and suggest that the processes of phototransduction may differ correspondingly in rods and cones.     

Maintenance of normal in situ chromosomal features in long-term tissue cultures

Clonal isolates from a rapidly proliferating fibroblast-like derivative have retained the classic diploid chromosome relationship over a period of many transplant generations. The readily identified members of the 11 pairs of chromosomes, including the sex chromosomes (X(1) and X(2)), have aided in localizing minute structural alterations within recloned diploid and aneuploid sublines.     

Inhibition of leishmanias but not host macrophages by the antitubulin herbicide trifluralin

The dinitroaniline herbicide trifluralin (alpha, alpha, alpha-trifluoro-2,6-dinitro-N, N-dipropyl-p-toluidine), at micromolar concentrations, selectively inhibited both proliferation and differentiation of the parasitic protozoan Leishmania mexicana amazonensis. In vitro, radioactive trifluralin showed specific binding to leishmania tubulin but not to mammalian tubulin. Because herbicides such as trifluralin are economical and are considered safe for man and domesticated animals, they may serve as useful sources of potential antiparasitic agents.     

Empathy for pain involves the affective but not sensory components of pain

Our ability to have an experience of another's pain is characteristic of empathy. Using functional imaging, we assessed brain activity while volunteers experienced a painful stimulus and compared it to that elicited when they observed a signal indicating that their loved one--present in the same room--was receiving a similar pain stimulus. Bilateral anterior insula (AI), rostral anterior cingulate cortex (ACC), brainstem, and cerebellum were activated when subjects received pain and also by a signal that a loved one experienced pain. AI and ACC activation correlated with individual empathy scores. Activity in the posterior insula/secondary somatosensory cortex, the sensorimotor cortex (SI/MI), and the caudal ACC was specific to receiving pain. Thus, a neural response in AI and rostral ACC, activated in common for "self" and "other" conditions, suggests that the neural substrate for empathic experience does not involve the entire "pain matrix." We conclude that only that part of the pain network associated with its affective qualities, but not its sensory qualities, mediates empathy.     

Induction of mesoderm by a viral oncogene in early Xenopus embryos

During frog embryogenesis, mesoderm is specified in the equatorial region of the early embryo by a signal from the vegetal hemisphere. Prospective ectodermal cells dissected from the animal hemisphere can be respecified to form mesodermal tissues by recombination with vegetal tissue or by treatment with any of several polypeptide growth factors or growth factor-like molecules. Together with the discovery that several developmental mutations in Drosophila are in genes with significant homology to mammalian mitogens and oncogenes, these observations suggest that early developmental signals may use similar transduction pathways to mitogenic signals characterized in cultured mammalian cells. Whether mesoderm can be induced by activation of intracellular signal transduction pathways implicated in mitogenesis and oncogenesis has been investigated with the viral oncogene polyoma middle T. Microinjection of middle T messenger RNA into early embryos results in the respecification of isolated prospective ectodermal tissue to form characteristic mesodermal structures. Middle T in frog blastomeres appears to associate with cellular activities similar to those observed in polyoma-transformed mouse cells, and transformation-defective middle T mutants fail to induce mesoderm. These results suggest that early inductive signals and mitogenic and oncogenic stimuli may share common signal transduction pathways.     

Gene amplification of c-myc and N-myc in small cell carcinoma of the lung

The relationship of the copy numbers of the c-myc and N-myc oncogenes to tumor formation and progression was studied in small cell carcinoma of the lung. When 96 neoplastic lesions from 45 patients were examined, these lesions could be grouped into three categories: high copy (tumors with greater than 3 copies of the N-myc or c-myc gene per haploid genome), middle copy (1.5 to 3 copies per genome), and normal copy. Fourteen of the patients had middle copy tumors, but this was almost always a result of chromosome duplication rather than the amplification of a small genetic locus. In contrast, five patients had high copy tumors, with the increased copy number in each case due to gene amplification. The amplification did not occur in a heterogeneous fashion within individual patients, since all metastatic lesions from patients with high copy lung tumors were also high copy, while none of 41 metastatic lesions from the other patients were high copy. These data suggest that gene amplification is an important step in neoplastic growth in a subset of patients with small cell carcinoma of the lung and that this genetic event occurs relatively early (before metastasis) in this subset.     

正常木与应压木木材形成组织中差异表达蛋白质的鉴定

为了鉴定应压木木材细胞壁形成中的差异表达蛋白质,并确定其在木材形成中的功能,采用双向差异凝胶电 泳技术,对正常木和应压木木材形成组织中蛋白质进行分离和鉴定,获得了较高质量的双向凝胶电泳图谱。应用 TOF-MS/ MS 技术对应压木和正常木木材形成组织中的差异表达蛋白质进行鉴定,并用MASCOT 软件对每个差异 点的匹配峰值在Swiss Prot 数据库中进行检索,最终确定了7 个差异蛋白质。其中,4 个蛋白质在应压木中表达上 调,3 个表达下调。这些蛋白质参与了木质素生物合成、应力响应与胁迫、细胞骨架运动及脂类代谢,因而推测它们 与应压木木材的形成有关。      

Attention but not awareness modulates the BOLD signal in the human V1 during binocular suppression

Although recent psychophysical studies indicate that visual awareness and top-down attention are two distinct processes, it is not clear how they are neurally dissociated in the visual system. Using a two-by-two factorial functional magnetic resonance imaging design with binocular suppression, we found that the visibility or invisibility of a visual target led to only nonsignificant blood oxygenation level-dependent (BOLD) effects in the human primary visual cortex (V1). Directing attention toward and away from the target had much larger and robust effects across all study participants. The difference in the lower-level limit of BOLD activation between attention and awareness illustrates dissociated neural correlates of the two processes. Our results agree with previously reported V1 BOLD effects on attention, while they invite a reconsideration of the functional role of V1 in visual awareness.