Role of Cancer Stem-like Cells in the Process of Invasion and Mesenchymal Transformation by a Reconstituted Triple-negative Breast Cancer Cell Population Resistant to p53-induced Apoptosis.

We investigated the role of cancer stem cells (CSCs) in a population of triple-negative breast cancer (TNBC) cells that are resistant to apoptosis. A human breast cancer cell population capable of inducing p53 expression with doxycycline (Dox) was created and used as an untreated control (UT). After the addition of Dox to UT for 5 days, the cell population reconstituted with cells showing resistance to apoptosis was named RE. Fluorescence-activated cell sorting (FACS) and immunostaining revealed that after the addition of Dox, the ratio of cells in the S and G2/M phases decreased in UT as apoptosis proceeded, but did not markedly change in apoptosis-resistant RE. CSC-like cells in RE exhibited a cell morphology with a larger ratio of the major/minor axis than UT. FACS showed that RE had a higher proportion of CSC-like cells and contained more CD44+CD24- mesenchymal CSCs than ALDH1A3+ epithelial-like CSCs. In a Matrigel invasion assay, UT was more likely to form a three-dimensional cell population, whereas RE exhibited a planar population, higher migration ability, and the up-regulated expression of epithelial-mesenchymal transition-related genes. These results provide insights into the mechanisms by which TNBC cells acquire treatment resistance at the time of recurrence.

Subjective health awareness and sensory ability of taste and olfaction: A case study of a health promotion class for older people.

The quality of the dietary habits of older adults is important for increasing healthy life expectancy. As with other physical senses, the senses of taste and olfaction change with age. In contrast to physical sensations that can be visibly compared with those of other people, taste and olfaction are personal sensations, making it challenging to infer associated changes. This study investigated the characteristics of taste and olfaction in healthy older adults and compared them with those of young adults. In the taste assessment, threshold values were measured using the whole-mouth method with a diagnostic assay kit (Tastedisc). The olfactory assessment measured the overall identification ability using a card-type olfactory identification test kit (Open Essence). Additionally, participants' subjective health awareness was measured using a visual analog scale. The taste and olfactory assessments results showed that the older group had lower overall sensory sensitivity than the young group, and that there was no correlation between taste and olfactory sensitivity in the older group, while a trend was observed in the young group. Moreover, there was no significant difference between the two groups regarding subjective health awareness, indicating that participants in our research considered themselves healthy regardless of age. This suggests that the subjective health awareness of older people in the health promotion class is somehow independent from their sensory ability.

Stem-like Human Breast Cancer Cells Initiate Vasculogenic Mimicry on Matrigel.

Vasculogenic mimicry (VM), referring to vasculogenic structures lined by tumor cells, can be distinguished from angiogenesis, and is responsible for the aggressiveness and metastatic potential of tumors. HCC1937/p53 cells were derived from triple-negative breast cancer (TNBC), and used to investigate the roles of breast cancer stem cells (CSCs) in the formation of VM. HCC1937/p53 cells formed mesh-like structures on matrigel culture in which expression of VM-related genes, vascular endothelial (VE)-cadherin, matrix metalloproteinase (MMP)-2 and MMP-9 was confirmed by droplet digital polymerase chain reaction (PCR). In immunofluorescence microscopy, aldehyde dehydrogenase (ALDH)1A3+ cells with properties of CSCs or progenitors and GATA binding protein 3 (GATA3)+ cells with more differentiated characteristics were localized in the bridging region and aggregated region of VM structures, respectively. In fluorescence-activated cell sorting analysis, ALDH+ cells, considered to be a subpopulation of CSCs sorted by the aldefluor assay, exhibited marked VM formation on matrigel in 24 hr, whereas ALDH- cells did not form VM, indicating possible roles of CSCs in VM formation. The stem-like cancer cells resistant to p53-induced apoptosis, which expressed a high rate of ALDH1A3 and Sex-determining region Y (SRY)-box binding protein-2 (Sox-2), completed VM formation much faster than the control. These findings may provide clues to elucidate the significance of VM formed by treatment-resistant CSCs in the metastatic potential and poor prognosis associated with TNBC.

An observation of a severely disabled infant chimpanzee in the wild and her interactions with her mother.

We report the physical and behavioral development of one severely disabled female infant chimpanzee (Pan troglodytes schweinfurthii) of the well-habituated M group in the Mahale Mountains National Park. We documented interactions between the infant and its mother and with other group members. Congenital disabilities occur in many primate species, including chimpanzees. However, there have been only a few case studies of congenitally disabled chimpanzee infants and no reports examining how a chimpanzee mother copes with such a disabled infant in the wild. The observed infant exhibited symptoms resembling Down syndrome, similar to those reported previously for a captive chimpanzee. The mother did not allow nonrelatives to take care of the infant even though she had been previously relatively tolerant of allomothering by nonrelatives. The mother's compensatory care for her infant's disabilities and allomothering of the infant by its sister might have helped it to survive for 23 months in the wild. Other group members did not show any aversive or fearful reactions to the disabled infant.

Death of the alpha: within-community lethal violence among chimpanzees of the Mahale Mountains National Park.

Chimpanzees (Pan troglodytes) are capable of extreme violence. They engage in inter-group, sometimes lethal, aggression that provides the winners with an opportunity to enlarge their territory, increase their food supply and, potentially, attract more mates. Lethal violence between adult males also occurs within groups but this is rare; to date, only four cases (three observed and one inferred) have been recorded despite decades of observation. In consequence, the reasons for within-group lethal violence in chimpanzees remain unclear. Such aggression may be rare due to the importance of coalitions between males during inter-group encounters; cooperation between males is also thought to be key in the defense or advancement of social rank within the group. Previous accounts of within-group lethal violence concern victims who were low-ranking males; here we provide the first account of the killing of an incumbent alpha male by a coalition of adult males from the same community. We found no clear evidence that the alpha male's position was under threat during the months before the lethal attack: the male dominance hierarchy was highly stable, with low rates of male-male aggression, and there were no significant changes in social interactions (i.e. grooming and aggression) between the alpha male and the other adult males. Two of the four attackers were former alpha males and were the individuals with whom the victim appeared, in the period preceding his death, to be most strongly affiliated: his most frequent grooming partners and those with whom he spent most time in proximity. The lethal attack triggered a period of instability in the male hierarchy and was likely an opportunistic attempt to seize alpha status by the third-ranking male.

Correlation between menstrual cycle and cognitive performance in a chimpanzee (Pan troglodytes).

Extensive research on human subjects has tried to investigate whether there is a correlation between cognitive performance and the menstrual cycle. Less is known about the relationship between the menstrual cycle and task performance in other cognitive animals. We test whether the secretion of a sex hormone [luteinizing hormone(LH)] influences the performance of cognitive tasks by a female chimpanzee (Pan troglodytes) who is part of a long-term cognition research program. We focus on two cognitive tasks: an "easy task," which consists of simple numerical ordering, and a "difficult task," which combines numerical ordering with memorizing the numerals' spatial location. Data on the performance of these cognitive tasks, urine samples, and sexual swelling over six menstrual cycles showed that the chimpanzee's performance accuracy decreased and that the intertrial interval was longer during the LH-surge of the menstrual cycle, but only for the performance of the difficult task. These performance attributes seem to reflect a decrease in attention or motivation during ovulation. In summary, the cognitive performance of a chimpanzee was disturbed by hormonal changes despite her long-term experience in the tasks.

Acquisition and memory of sequence order in young and adult chimpanzees (Pan troglodytes).

There is no research about age difference in the process of sequential learning in non-human primates. Is there any difference between young and adults in sequential learning process? Six chimpanzees (Pan troglodytes), 3 young and 3 adults, learned the Arabic numeral sequence 1 to 9 by touching the numerals on a touch-screen monitor in ascending order. Initially, the sequence always started with the numeral 1, i.e. 'start-fixed task'. Training began with the sequence 1-2, 1-2-3, and continued sequentially up to 1-2-3-4-5-6-7-8-9. Later, the subjects were introduced to sequences that started with a random numeral, but always ended with 9, i.e. 'end-fixed task'. Performance in the end-fixed task was worse relative to the familiar start-fixed task. After training with various sequences of adjacent numerals, the subjects were given a transfer test for the non-adjacent numerals. The results suggested that all chimpanzees indeed mastered sequential ordering, and although there was no fundamental difference in the acquisition process between the two age groups, there was a significant age difference in memory capacity. Based on their knowledge of sequential ordering, the subjects were then asked to perform a masking task in which once a subject touched the lowest numeral, the other numeral(s) turned to white squares. Performance of the masking task by young chimpanzees was better than that of adults in accuracy and degree of difficulty (number of numerals). Taken together, these data clearly demonstrate a similarity among subjects in the way chimpanzees acquire knowledge of sequential order regardless of age differences in sequential learning. Moreover, they reveal that once knowledge of sequential order is established, it can be a good index used to evaluate memory capacity in young and adult chimpanzees.

Family resemblances facilitate formation and expansion of functional equivalence classes in pigeons.

Four pigeons were given repeated reversal training and testing with photographs of human faces constituting two categories structured by family resemblances, each consisting of a prototype, good exemplars, and poor exemplars. Each of the good exemplars (AM, BM, and CM) was created by 50% morphing of the prototype (M) and one of the poor exemplars (A, B, and C, respectively) and thus was physically similar to the prototype and to the corresponding poor exemplar. The pigeons were first trained and tested for the formation of two (AM, BM, and CM) classes. Then, the stimulus sets were extended to include (1) M and the poor exemplars that were not physically similar to one another and (2) 50% morphs of the poor exemplars (AB, BC, and CA). In the sequentially introduced training and test phases, we successfully tracked expansion of the functional equivalence classes consisting of exemplars that had little similarity but could be linked together through other members of the class.

Pigeon's recognition of cartoons: effects of fragmentation, scrambling, and deletion of elements.

J. Cerella [Pattern Recognit. 12 (1980) 1] and more recently S. Watanabe [Behav. Proc. 53 (2001) 3] demonstrated that pigeons showed no decrement in recognizing cartoons that were spatially scrambled, indicating that pigeons' discriminative responding is controlled by local features alone. In contrast Kirkpatrick-Steger et al. [J. Exp. Psychol. Anim. Behav. Proc. 24 (1998) 34] used line drawings as stimuli and demonstrated the importance of spatial organization for picture recognition by pigeons, confirming related findings reported in their previous studies. The present study revisited the recognition of cartoons by pigeons. In Experiment 1, pigeons were trained to discriminate cartoon people on a variety of background scenes. Subsequent tests revealed that discriminative performances with both familiar and novel instances decreased as the objects and object-like parts were progressively fragmented, indicating that search for the targeted cartoon people in the stimulus array might have enhanced the pigeons to attend to global aspects of cartoon people. Experiment 2 used line drawings of cartoon faces as stimuli and examined effects of scrambling and deletion of components. A set of components (eyes and eyebrows) exerted strong control over behavior and scrambling only moderately suppressed responding. The results suggest that pigeons use both global and local aspects, with different mixtures of these types of information depending on the particular perceptual context.