bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensively duplicated and transcriptionally active recent lateral gene transfer from a bacterial Wolbachia endosymbiont to its host filarial nematode Brugia malayi
Authors: Ioannidis Panagiotis , Johnston Kelly L , Riley David R , Kumar Nikhil , White James R , Olarte Karen T , Ott Sandra , Tallon Luke J , Foster Jeremy M , Taylor Mark J , Dunning Hotopp Julie C 
Published: September 2013

Abstract

Background
Lymphatic filariasis is a neglected tropical disease afflicting more than 120 million people, while another 1.3 billion people are at risk of infection. The nematode worm Brugia malayi is one of the causative agents of the disease and exists in a mutualistic symbiosis with Wolbachia bacteria. Since extensive lateral gene transfer occurs frequently between Wolbachia and its hosts, we sought to measure the extent of such LGT in B. malayi by whole genome sequencing of Wolbachia-depleted worms.

Results
A considerable fraction (at least 115.4-kbp, or 10.6%) of the 1.08-Mbp Wolbachia w Bm genome has been transferred to its nematode host and retains high levels of similarity, including 227 w Bm genes and gene fragments. Complete open reading frames were transferred for 32 of these genes, meaning they have the potential to produce functional proteins. Moreover, four transfers have evidence of life stage-specific regulation of transcription at levels similar to other nematode transcripts, strengthening the possibility that they are functional.

Conclusions
There is extensive and ongoing transfer of Wolbachia DNA to the worm genome and some transfers are transcribed in a stage-specific manner at biologically relevant levels.
Comparative genomics reveals distinct host-interacting traits of three major human-associated propionibacteria
Authors: Mak Tim N , Schmid Monika , Brzuszkiewicz Elzbieta , Zeng Guanghong , Meyer Rikke , Sfanos Karen S , Brinkmann Volker , Meyer Thomas F , Brüggemann Holger 
Published: September 2013

AbstractBackgroundPropionibacteria are part of the human microbiota. Many studies have addressed the predominant colonizer of sebaceous follicles of the skin,Propionibacterium acnes, and investigated its association with the skin disorder acne vulgaris, and lately with prostate cancer. Much less is known about two other propionibacterial species frequently found on human tissue sites,Propionibacterium granulosumandPropionibacterium avidum. Here we analyzed two and three genomes ofP. granulosumandP. avidum, respectively, and compared them to two genomes ofP. acnes; we further highlight differences among the three cutaneous species with proteomic and microscopy approaches.ResultsElectron and atomic force microscopy revealed an exopolysaccharide (EPS)-like structure surroundingP. avidumcells, that is absent inP. acnesandP. granulosum. In contrast,P. granulosumpossesses pili-like appendices, which was confirmed by surface proteome analysis. The corresponding genes were identified; they are clustered with genes encoding sortases. Both,P. granulosumandP. avidumlack surface or secreted proteins for predicted host-interacting factors ofP. acnes, including several CAMP factors, sialidases, dermatan-sulphate adhesins, hyaluronidase and a SH3 domain-containing lipoprotein; accordingly, onlyP. acnesexhibits neuraminidase and hyaluronidase activities. These functions are encoded on previously unrecognized island-like regions in the genome ofP. acnes.ConclusionsDespite their omnipresence on human skin little is known about the role of cutaneous propionibacteria. All three species are associated with a variety of diseases, including postoperative and device-related abscesses and infections. We showed that the three organisms have evolved distinct features to interact with their human host. WhereasP. avidumandP. granulosumproduce an EPS-like surface structure and pili-like appendices, respectively,P. acnespossesses a number of unique surface-exposed proteins with host-interacting properties. The different surface properties of the three cutaneous propionibacteria are likely to determine their colonizing ability and pathogenic potential on the skin and at non-skin sites.
Prothymosin α and a prothymosin α-derived peptide enhance TH1-type immune responses against defined HER-2/neu epitopes
Authors: Ioannou Kyriaki , Derhovanessian Evelyna , Tsakiri Eleni , Samara Pinelopi , Kalbacher Hubert , Voelter Wolfgang , Trougakos Ioannis P , Pawelec Graham , Tsitsilonis Ourania E 
Published: September 2013

AbstractBackgroundActive cancer immunotherapies are beginning to yield clinical benefit, especially those using peptide-pulsed dendritic cells (DCs). Different adjuvants, including Toll-like receptor (TLR) agonists, commonly co-administered to cancer patients as part of a DC-based vaccine, are being widely tested in the clinical setting. However, endogenous DCs in tumor-bearing individuals are often dysfunctional, suggesting thatex vivoeducated DCs might be superior inducers of anti-tumor immune responses. We have previously shown that prothymosin alpha (proTα) and its immunoreactive decapeptide proTα(100–109) induce the maturation of human DCsin vitro.The aim of this study was to investigate whether proTα- or proTα(100–109)-matured DCs are functionally competent and to provide preliminary evidence for the mode of action of these agents.ResultsMonocyte-derived DCs maturedin vitrowith proTα or proTα(100–109) express co-stimulatory molecules and secrete pro-inflammatory cytokines. ProTα- and proTα(100–109)-matured DCs pulsed with HER-2/neu peptides induce TH1-type immune responses, prime autologous naïve CD8-positive (+) T cells to lyse targets expressing the HER-2/neu epitopes and to express a polyfunctional profile, and stimulate CD4+ T cell proliferation in an HER-2/neu peptide-dependent manner. DC maturation induced by proTα and proTα(100–109) is likely mediatedviaTLR-4, as shown by assessing TLR-4 surface expression and the levels of the intracellular adaptor molecules TIRAP, MyD88 and TRIF.ConclusionsOur results suggest that proTα and proTα(100–109) induce both the maturation and the T cell stimulatory capacity of DCs. Although further studies are needed, evidence for a possible proTα and proTα(100–109) interaction with TLR-4 is provided. The initial hypothesis that proTα and the proTα-derived immunoactive decapeptide act as “alarmins”, provides a rationale for their eventual use as adjuvants in DC-based anti-cancer immunotherapy.
Decreased striatal dopamine in group II metabotropic glutamate receptor (mGlu2/mGlu3) double knockout mice
Authors: Lane Tracy A , Boerner Thomas , Bannerman David M , Kew James NC , Tunbridge Elizabeth M , Sharp Trevor , Harrison Paul J 
Published: September 2013

Abstract

Background
Group II metabotropic glutamate receptors (mGlu2 and mGlu3, encoded by Grm2 and Grm3) have been the focus of attention as treatment targets for a number of psychiatric conditions. Double knockout mice lacking mGlu2 and mGlu3 (mGlu2/3−/−) show a subtle behavioural phenotype, being hypoactive under basal conditions and in response to amphetamine, and with a spatial memory deficit that depends on the arousal properties of the task. The neurochemical correlates of this profile are unknown. Here, we measured tissue levels of dopamine, 5-HT, noradrenaline and their metabolites in the striatum and frontal cortex of mGlu2/3−/− double knockout mice, using high performance liquid chromatography. We also measured the same parameters in mGlu2−/− and mGlu3−/− single knockout mice.

Results
mGlu2/3−/−mice had reduced dopamine levels in the striatum but not in frontal cortex, compared to wild-types. In a separate cohort we replicated this deficit and, using tissue punches, found it was more prominent in the nucleus accumbens than in dorsolateral striatum. Noradrenaline, 5-HT and their metabolites were not altered in the striatum of mGlu2/3−/− mice, although the noradrenaline metabolite MHPG was increased in the cortex. In mGlu2−/− and mGlu3−/− single knockout mice we found no difference in any monoamine or metabolite, in either brain region, compared to their wild-type littermates.

Conclusions
Group II metabotropic glutamate receptors impact upon striatal dopamine. The effect may contribute to the behavioural phenotype of mGlu2/3−/− mice. The lack of dopaminergic alterations in mGlu2−/− and mGlu3−/− single knockout mice reveals a degree of redundancy between the two receptors. The findings support the possibility that interactions between mGlu2/3 and dopamine may be relevant to the pathophysiology and therapy of schizophrenia and other disorders.
A novel RNA binding protein affects rbcL gene expression and is specific to bundle sheath chloroplasts in C4plants
Authors: Bowman Shaun M , Patel Minesh , Yerramsetty Pradeep , Mure Christopher M , Zielinski Amy M , Bruenn Jeremy A , Berry James O 
Published: September 2013

Abstract

Background
Plants that utilize the highly efficient C4 pathway of photosynthesis typically possess kranz-type leaf anatomy that consists of two morphologically and functionally distinct photosynthetic cell types, the bundle sheath (BS) and mesophyll (M) cells. These two cell types differentially express many genes that are required for C4 capability and function. In mature C4 leaves, the plastidic rbcL gene, encoding the large subunit of the primary CO2 fixation enzyme Rubisco, is expressed specifically within BS cells. Numerous studies have demonstrated that BS-specific rbcL gene expression is regulated predominantly at post-transcriptional levels, through the control of translation and mRNA stability. The identification of regulatory factors associated with C4 patterns of rbcL gene expression has been an elusive goal for many years.

Results
RLSB, encoded by the nuclear RLSB gene, is an S1-domain RNA binding protein purified from C4 chloroplasts based on its specific binding to plastid-encoded rbcL mRNA in vitro. Co-localized with LSU to chloroplasts, RLSB is highly conserved across many plant species. Most significantly, RLSB localizes specifically to leaf bundle sheath (BS) cells in C4 plants. Comparative analysis using maize (C4) and Arabidopsis (C3) reveals its tight association with rbcL gene expression in both plants. Reduced RLSB expression (through insertion mutation or RNA silencing, respectively) led to reductions in rbcL mRNA accumulation and LSU production. Additional developmental effects, such as virescent/yellow leaves, were likely associated with decreased photosynthetic function and disruption of associated signaling networks.

Conclusions
Reductions in RLSB expression, due to insertion mutation or gene silencing, are strictly correlated with reductions in rbcL gene expression in both maize and Arabidopsis. In both plants, accumulation of rbcL mRNA as well as synthesis of LSU protein were affected. These findings suggest that specific accumulation and binding of the RLSB binding protein to rbcL mRNA within BS chloroplasts may be one determinant leading to the characteristic cell type-specific localization of Rubisco in C4 plants. Evolutionary modification of RLSB expression, from a C3 “default” state to BS cell-specificity, could represent one mechanism by which rbcL expression has become restricted to only one cell type in C4 plants.
Involvement of ethylene biosynthesis and signalling in fruit set and early fruit development in zucchini squash (Cucurbita pepoL.)
Authors: Martínez Cecilia , Manzano Susana , Megías Zoraida , Garrido Dolores , Picó Belén , Jamilena Manuel 
Published: September 2013

Abstract

Background
We have identified a kind of parthenocarpy in zucchini squash which is associated with an incomplete andromonoecy, i.e. a partial conversion of female into bisexual flowers. Given that andromonoecy in this and other cucurbit species is caused by a reduction of ethylene production in the female flower, the associated parthenocarpic development of the fruit suggested the involvement of ethylene in fruit set and early fruit development.

Results
We have compared the production of ethylene as well as the expression of 13 ethylene biosynthesis and signalling genes in pollinated and unpollinated ovaries/fruits of two cultivars, one of which is parthenocarpic (Cavili), while the other is non-parthenocarpic (Tosca). In the latter, unpollinated ovaries show an induction of ethylene biosynthesis and ethylene signal transduction pathway genes three days after anthesis, which is concomitant with the initiation of fruit abortion and senescence. Fruit set and early fruit development in pollinated flowers of both cultivars and unpollinated flowers of Cavili is coupled with low ethylene biosynthesis and signalling, which would also explain the partial andromonoecy in the parthenocarpic genotype. The reduction of ethylene production in the ovary cosegregates with parthenocarpy and partial andromonoecy in the selfing progeny of Cavili. Moreover, the induction of ethylene in anthesis (by ethephon treatments) reduced the percentage of bisexual parthenocarpic flowers in Cavili, while the inhibition of ethylene biosynthesis or response (by AVG and STS treatments) induces not only andromonoecy but also the parthenocarpic development of the fruit in both cultivars.

Conclusions
Results demonstrate that a reduction of ethylene production or signalling in the zucchini flower is able to induce fruit set and early fruit development, and therefore that ethylene is actively involved in fruit set and early fruit development. Auxin and TIBA treatments, inducing fruit set and early fruit development in this species, also inhibit ethylene production and the expression of ethylene biosynthesis and response genes. A model is presented that discusses the crosstalk between ethylene and auxin in the control of fruit set and early fruit development in zucchini squash.
Klebsiella pneumoniae bacteremia and renosplenic abscesses without intestinal symptoms as the initial manifestations of non-steroidal anti-inflammatory drug-induced colitis: a rare case report
Authors: Huang Hung-Ling , Lu Po-Liang , Lin Chun-Yu , Chen Yen-Hsu , Kuo Chao-Hung , Lin Wei-Ru 
Published: September 2013

Abstract

Background
Non-steroidal anti-inflammatory drugs (NSAIDs), the most widely prescribed drugs in the world, can cause gastrointestinal damage, including colitis. However, the prevalence of NSAID-induced colitis is unknown because the disease is often asymptomatic.

Case presentation
We report the case of a 64-year-old female patient with a history of long-term NSAID use, who was hospitalized with septic shock caused by Klebsiella pneumoniae bacteremia. Computed tomography revealed multiple renal and splenic abscesses with diffuse colon wall thickening. A colonoscopy confirmed colitis with diffuse ulcers. NSAIDs were discontinued after this hospitalization. The abscesses improved after antibiotic treatment. A short course of balsalazide treatment was given under the suspicion of ulcerative colitis. Balsalazide was discontinued four months later due to a non-compatible clinical course. A follow-up colonoscopy two years later revealed a normal colon mucosa, and NSAID-induced colitis was diagnosed.

Conclusion
This is the first reported case of combined bacterial splenic and renal abscesses without intestinal manifestations as the initial presentation of NSAID-induced colitis. In contrast to cases of K. pneumoniae bacteremia with primary liver abscesses in patients with diabetes mellitus in Taiwan, we presented the first case with abscesses caused by community-acquired K. pneumoniae in the kidneys and spleen without liver invasion. In conclusion, our case report alerts clinicians to the possibility that K. pneumoniae bacteremia combined with multiple abscesses can be associated with severe NSAID-induced colitis.
OTOF mutation screening in Japanese severe to profound recessive hearing loss patients
Authors: Iwasa Yoh-ichiro , Nishio Shin-ya , Yoshimura Hidekane , Kanda Yukihiko , Kumakawa Kozo , Abe Satoko , Naito Yasushi , Nagai Kyoko , Usami Shin-ichi 
Published: September 2013

Abstract

Background
Auditory neuropathy spectrum disorder (ANSD) is a unique form of hearing loss that involves absence or severe abnormality of auditory brainstem response (ABR), but also the presence of otoacoustic emissions (OAEs). However, with age, the OAEs disappear, making it difficult to distinguish this condition from other nonsyndromic hearing loss. Therefore, the frequency of ANSD may be underestimated. The aim of this study was to determine what portion of nonsyndromic hearing loss is caused by mutations of OTOF, the major responsible gene for nonsyndromic ANSD.

Methods
We screened 160 unrelated Japanese with severe to profound recessive nonsyndromic hearing loss (ARNSHL) without GJB2 or SLC26A4 mutations, and 192 controls with normal hearing.

Results
We identified five pathogenic OTOF mutations (p.D398E, p.Y474X, p.N727S, p.R1856Q and p.R1939Q) and six novel, possibly pathogenic variants (p.D450E, p.W717X, p.S1368X, p.R1583H, p.V1778I, and p.E1803A).

Conclusions
The present study showed that OTOF mutations accounted for 3.2–7.3% of severe to profound ARNSHL patients in Japan. OTOF mutations are thus a frequent cause in the Japanese deafness population and mutation screening should be considered regardless of the presence/absence of OAEs.
Intestinal-type of differentiation predicts favourable overall survival: confirmatory clinicopathological analysis of 198 periampullary adenocarcinomas of pancreatic, biliary, ampullary and duodenal origin
Authors: Bronsert Peter , Kohler Ilona , Werner Martin , Makowiec Frank , Kuesters Simon , Hoeppner Jens , Hopt Ulrich Theodor , Keck Tobias , Bausch Dirk , Wellner Ulrich Friedrich 
Published: September 2013

Abstract

Background
Periampullary adenocarcinomas comprise pancreatic, distal bile duct, ampullary and duodenal adenocarcinoma. The epithelia of these anatomical structures share a common embryologic origin from the foregut. With steadily increasing numbers of pancreatoduodenectomies over the last decades, pathologists, surgeons and oncologists are more often confronted with the diagnosis of “other than pancreatic” periampullary cancers. The intestinal subtype of ampullary cancer has been shown to correlate with better prognosis.

Methods
Histological subtype and immunohistochemical staining pattern for CK7, CK20 and CDX2 were assessed for n = 198 cases of pancreatic ductal, distal bile duct, ampullary and duodenal adenocarcinoma with clinical follow-up. Routine pathological parameters were included in survival analysis performed with SPSS 20.

Results
In univariate analysis, intestinal subtype was associated with better survival in ampullary, pancreatic ductal and duodenal adenocarcinoma. The intestinal type of pancreatic ductal adenocarcinoma was not associated with intraductal papillary mucinous neoplasm and could not be reliably diagnosed by immunohistochemical staining pattern alone. Intestinal differentiation and lymph node ratio, but not tumor location were independent predictors of survival when all significant predictor variables from univariate analysis (grade, TNM stage, presence of precursor lesions, surgical margin status, perineural, vascular and lymphatic vessel invasion, CK7 and CDX2 staining pattern) were included in a Cox proportional hazards model.

Conclusions
Intestinal type differentiation and lymph node ratio but not tumor location are independent prognostic factors in pooled analysis of periampullary adenocarcinomas. We conclude that differentiation is more important than tumor location for prognostic stratification in periampullary adenocarcinomas.
BMP4 inhibits the proliferation of breast cancer cells and induces an MMP-dependent migratory phenotype in MDA-MB-231 cells in 3D environment
Authors: Ampuja Minna , Jokimäki Riikka , Juuti-Uusitalo Kati , Rodriguez-Martinez Alejandra , Alarmo Emma-Leena , Kallioniemi Anne 
Published: September 2013

Abstract

Background
Bone morphogenetic protein 4 (BMP4) belongs to the transforming growth factor β (TGF-β) family of proteins. BMPs regulate cell proliferation, differentiation and motility, and have also been reported to be involved in cancer pathogenesis. We have previously shown that BMP4 reduces breast cancer cell proliferation through G1 cell cycle arrest and simultaneously induces migration in a subset of these cell lines. Here we examined the effects of BMP4 in a more physiological environment, in a 3D culture system.

Methods
We used two different 3D culture systems; Matrigel, a basement membrane extract from mouse sarcoma cells, and a synthetic polyethylene glycol (PEG) gel. AlamarBlue reagent was used for cell proliferation measurements and immunofluorescence was used to determine cell polarity. Expression of cell cycle regulators was examined by Western blot and matrix metalloproteinase (MMP) expression by qRT-PCR.

Results
The MCF-10A normal breast epithelial cells formed round acini with correct apicobasal localization of α6 integrin in Matrigel whereas irregular structures were seen in PEG gel. The two 3D matrices also supported dissimilar morphology for the breast cancer cells. In PEG gel, BMP4 inhibited the growth of MCF-10A and the three breast cancer cell lines examined, thus closely resembling the 2D culture conditions, but in Matrigel, no growth inhibition was observed in MDA-MB-231 and MDA-MB-361 cells. Furthermore, BMP4 induced the expression of the cell cycle inhibitor p21 both in 2D and 3D culture, thereby partly explaining the growth arrest. Interestingly, MDA-MB-231 cells formed large branching, stellate structures in response to BMP4 treatment in Matrigel, suggestive of increased cell migration or invasion. This effect was reversed by Batimastat, a broad-spectrum MMP inhibitor, and subsequent analyses showed BMP4 to induce the expression of MMP3 and MMP14, that are thus likely to be responsible for the stellate phenotype.

Conclusions
Taken together, our results show that Matrigel provides a more physiological environment for breast epithelial cells than PEG gel. Moreover, BMP4 partly recapitulates in 3D culture the growth suppressive abilities previously seen in 2D culture and induces an MMP-dependent migratory phenotype in MDA-MB-231 cells.
Urinary 6-sulphatoxymelatonin levels in patients with senile cataracts
Authors: Akdogan Muberra , Budak Yasemin U , Huysal Kagan 
Published: September 2013

Abstract

Background
The antioxidant melatonin effectively scavenges highly toxic hydroxyl radicals. Decreases in circulating melatonin levels have been reported in patients with diseases that become more serious with advancing age. The purpose of the present study was to explore the relationship between circulatory melatonin level and the extent of senile cataracts. To this end, we assessed the urinary excretion levels of 6-sulphatoxymelatonin (aMTS6), a major metabolite of melatonin.

Methods
A total of 22 patients (aged 64 ± 7 years; 12 males and 10 females) with senile cataracts and 22 healthy controls (aged 61 ± 8 years, 12 males and 10 females) were studied. aMTS6 urine levels were measured using commercial ELISA kits. Each aMTS6 level was expressed as [aMTS6] (in ng)/[mg] creatinine. As the data were not normally distributed, the Mann–Whitney U-test was employed to assess the statistical validity of the difference observed.

Results
The aMT6 level in nocturnal urine was 17.87 ± 14.43 ng aMTS6/mg creatinine (mean ± SD) in senile cataract patients; this was 76% of the level measured in age- and gender-matched controls (23.28 ± 16.27 ng aMTS6/mg creatinine). This difference in nocturnal urine aMTS6 level between senile cataract patients and controls was not statistically significant (p = 0.358).

Conclusion
The urinary aMTS6 level did not differ between subjects with and without senile cataracts.