RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

RESUMEN

The lateral habenula (LHb) is a key brain region involved in the pathophysiology of depression. It is activated by stimuli associated with negative experiences and is involved in encoding aversive signals. Hyperactivity of LHb is found in both rodent models of depression and human patients with depression. However, little is known about the underlying molecular mechanisms. Here we show that in LHb neurons, p11, a multifunctional protein implicated in depression, is significantly upregulated by chronic restraint stress. Knockdown of p11 expression in LHb alleviates the stress-induced depression-like behaviors. Moreover, chronic restraint stress induces bursting action potentials in LHb neurons, which are abolished by p11 knockdown. Overexpression of p11 in dopamine D2 receptor-containing LHb neurons of control mice induces depression-like behaviors. These results have identified p11 in LHb as a key molecular determinant regulating negative emotions, which may help to understand the molecular and cellular basis of depression.

Asunto(s)

RESUMEN

Chronic stress has a crucial role in the development of psychiatric diseases, such as anxiety and depression. Dysfunction of the medial prefrontal cortex (mPFC) has been linked to the cognitive and emotional deficits induced by stress. However, little is known about the molecular and cellular determinants in mPFC for stress-associated mental disorders. Here we show that chronic restraint stress induces the selective loss of p11 (also known as annexin II light chain, S100A10), a multifunctional protein binding to 5-HT receptors, in layer II/III neurons of the prelimbic cortex (PrL), as well as depression-like behaviors, both of which are reversed by selective serotonin reuptake inhibitors (SSRIs) and the tricyclic class of antidepressant (TCA) agents. In layer II/III of the PrL, p11 is highly concentrated in dopamine D2 receptor-expressing (D2+) glutamatergic neurons. Viral expression of p11 in D2+ PrL neurons alleviates the depression-like behaviors exhibited by genetically manipulated mice with D2+ neuron-specific or global deletion of p11. In stressed animals, overexpression of p11 in D2+ PrL neurons rescues depression-like behaviors by restoring glutamatergic transmission. Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, which provides a framework for the development of new strategies to treat stress-associated mental illnesses.

Asunto(s)

RESUMEN

Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.

Asunto(s)

RESUMEN

Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

Asunto(s)

RESUMEN

Eleven distinct families of resistance gene analogs (RGAs) with the characteristic nucleotide-binding sequence (NBS) were identified in two wild apple species, Malus prunifolia and M. baccata, and two cultivated apple cultivars, M. domestica cv. Fuji and M. domestica cv. Hong-ok, using PCR approaches with degenerate primers based on two conserved motifs of known NBS-LRR resistance genes. These RGA families were found to be represented in all the apple species tested, including wild and cultivated species. However, their sequences are very divergent from each other. Furthermore, the low level of recombination detected within their RGA families supports the idea that the evolution of NBS-encoding sequences in apple species involves the gradual accumulation of mutations. Despite the high diversity of the RGA families found in all apple species, the apparent lack of differentiation between wild and cultivated forms suggests that other factors, such as the capacity to tolerate pathogens, might play an important role in the survival of wild-type species.

Asunto(s)

RESUMEN

A case-control study was performed to assess the potential influence of CYP19 Arg(264)Cys and CYP1B1 Leu(432)Val polymorphisms on breast cancer risk in a series of Korean breast cancer patients and controls. The results suggest that the CYP19 Arg(264)Cys polymorphism modifies breast cancer risk (OR=1.5, 95% CI=1.1-2.2), especially in association with alcohol consumption (P for interaction=0.04), whereas the CYP1B1 Leu(432)Val polymorphism appears to play no role here.

Asunto(s)

RESUMEN

A problem of acoustic wave scattering from two circular apertures in a thick hard plane is solved. The Hankel transform and mode matching is used to represent the scattered field in rapidly convergent series. The reflection coefficient, transmission coefficient, and far-zone field are rigorously derived and presented in numerically efficient forms. Numerical computations are performed to illustrate scattering behaviors in terms of aperture geometry.

RESUMEN

Inorganic zeolites are used for many practical applications that exploit the microporosity intrinsic to their crystal structures. Organic analogues, which are assembled from modular organic building blocks linked through non-covalent interactions, are of interest for similar applications. These range from catalysis, separation and sensor technology to optoelectronics, with enantioselective separation and catalysis being especially important for the chemical and pharmaceutical industries. The modular construction of these analogues allows flexible and rational design, as both the architecture and chemical functionality of the micropores can, in principle, be precisely controlled. Porous organic solids with large voids and high framework stability have been produced, and investigations into the range of accessible pore functionalities have been initiated. For example, catalytically active organic zeolite analogues are known, as are chiral metal-organic open-framework materials. However, the latter are only available as racemic mixtures, or lack the degree of framework stability or void space that is required for practical applications. Here we report the synthesis of a homochiral metal-organic porous material that allows the enantioselective inclusion of metal complexes in its pores and catalyses a transesterification reaction in an enantioselective manner. Our synthesis strategy, which uses enantiopure metal-organic clusters as secondary building blocks, should be readily applicable to chemically modified cluster components and thus provide access to a wide range of porous organic materials suitable for enantioselective separation and catalysis.