bluuebunny/crossref_metadata_2025_split huggingface dataset:
SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression
Authors: Xu Zhejun , Liang Qifei , Song Xiaolei , Zhang Zhuangzhi , Lindtner Susan , Li Zhenmeiyu , Wen Yan , Liu Guoping , Guo Teng , Qi Dashi , Wang Min , Wang Chunyang , Li Hao , You Yan , Wang Xin , Chen Bin , Feng Hua , Rubenstein John L. , Yang Zhengang 
Published: July 2018

ABSTRACT
Dopamine receptor DRD1-expressing medium spiny neurons (D1 MSNs) and dopamine receptor DRD2-expressing medium spiny neurons (D2 MSNs) are the principal projection neurons in the striatum, which is divided into dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle). Progenitors of these neurons arise in the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the transcription factor genes Sp8 and Sp9 lose virtually all D2 MSNs as a result of reduced neurogenesis in the LGE, whereas D1 MSNs are largely unaffected. SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Six3. Thus, this study defines components of a transcription pathway in a regionally restricted LGE progenitor domain that selectively drives the generation of D2 MSNs.
A carcinogenic trigger to study the function of tumor suppressor genes in Schmidtea mediterranea
Authors: Van Roten Andromeda , Barakat Amal Zohir Abo-Zeid , Wouters Annelies , Tran Thao Anh , Mouton Stijn , Noben Jean-Paul , Gentile Luca , Smeets Karen 
Published: July 2018

ABSTRACT
Planarians have been long known for their regenerative ability, which hinges on pluripotency. Recently, however, the planarian model has been successfully established for routine toxicological screens aimed to assess overproliferation, mutagenicity and tumorigenesis. In this study, we focused on planarian tumor suppressor genes (TSGs) and their role during chemically induced carcinogenic stress in Schmidtea mediterranea. Combining in silico and proteomic screens with exposure to human carcinogen type 1A agent cadmium (Cd), we showed that many TSGs have a function in stem cells and that, in general, exposure to Cd accelerated the onset and increased the severity of the observed phenotype. This suggested that the interaction between environmental and genetic factors plays an important role in tumor development in S. mediterranea. Therefore, we further focused on the synergistic effects of Cd exposure and p53 knockdown (KD) at the cellular and molecular levels. Cd also produced a specific proteomic landscape in homeostatic animals, with 172 proteins differentially expressed, 43 of which were downregulated. Several of these proteins have tumor suppressor function in human and other animals, namely Wilms Tumor 1 Associated Protein (WT1), Heat Shock Protein 90 (HSP90), Glioma Pathogenesis-Related Protein 1 (GLIPR1) and Matrix Metalloproteinase B (Smed-MMPB). Both Glipr1 and MmpB KD produced large outgrowths, epidermal lesions and epidermal blisters. The epidermal blisters that formed as a consequence of Smed-MmpB KD were populated by smedwi1+ cells, many of which were actively proliferating, while large outgrowths contained ectopically differentiated structures, such as photoreceptors, nervous tissue and a small pharynx. In conclusion, Smed-MmpB is a planarian TSG that prevents stem cell proliferation and differentiation outside the proper milieu.
HIF-1α activation in myeloid cells accelerates dextran sodium sulfate-induced colitis progression in mice
Authors: Kim Young-Eun , Lee Minji , Gu Hyejung , Kim Jeongwoo , Jeong Seongju , Yeo Sujin , Lee You Jeong , Im Sin-Hyeog , Sung Young-Chul , Kim Hak Jae , Weissman Irving L. , Ahn G-One 
Published: July 2018

ABSTRACT
Inflammatory bowel disease (IBD) is a chronic inflammatory disease, in which the intestinal epithelium loses its barrier function. Given the existence of the oxygen gradient in the intestinal epithelium and that inflammation further contributes to the tissue hypoxia, we investigated the role of hypoxia-inducible factor (HIF), a transcription factor activated under hypoxic conditions in myeloid cells, in the progression of IBD. To do this, we utilized myeloid-specific knockout (KO) mice targeting HIF pathways, created by a Cre-loxP system with human MRP8 (hMRP8), an intracellular calcium-binding protein, as the myeloid promoter. By feeding 5% dextran sodium sulfate (DSS) to hMRP8 von Hippel Lindau (Vhl) KO mice, in which HIF-1α and HIF-2α are constitutively activated in myeloid cells, we found that these mice were highly susceptible to DSS-induced colitis, demonstrating greater body weight loss, increased mortality, faster onset of rectal bleeding, shortened colon length, and increased CD11b- or Gr-1-positive myeloid cells in the colon compared with wild-type (WT) mice. These parameters were restored to, if not better than, the WT levels when we examined hMRP8 Hif-1a KO mice upon 5% DSS feeding. hMRP8 Hif-2a KO mice, on the other hand, exhibited a similar degree of DSS-induced colitis to that of WT mice. Lastly, when DSS was given together with azoxymethane to induce tumorigenesis in the colon, we found that hMRP8 Hif-1a KO mice exhibited comparable levels of colorectal tumors to those of WT mice, indicating that HIF-1α in myeloid cells is dispensable for tumorigenesis. Collectively, our results suggest that HIF-1α activation in myeloid cells critically regulates IBD progression.
Switch-like PKA responses in the nucleus of striatal neurons
Authors: Yapo Cédric , Nair Anu G. , Hellgren Kotaleski Jeanette , Vincent Pierre , Castro Liliana R. V. 
Published: July 2018

ABSTRACT
Although it is known that protein kinase A (PKA) in the nucleus regulates gene expression, the specificities of nuclear PKA signaling remain poorly understood. Here, we combined computational modeling and live-cell imaging of PKA-dependent phosphorylation in mouse brain slices to investigate how transient dopamine signals are translated into nuclear PKA activity in cortical pyramidal neurons and striatal medium spiny neurons. We observed that the nuclear PKA signal in striatal neurons featured an ultrasensitive responsiveness, associated with fast all-or-none responses, which is not consistent with the commonly accepted theory of a slow and passive diffusion of catalytic PKA in the nucleus. Our numerical model suggests that a positive feed-forward mechanism inhibiting nuclear phosphatase activity – possibly mediated by DARPP-32 (also known as PPP1R1B) – could be responsible for this non-linear pattern of nuclear PKA response, allowing for a better detection of the transient dopamine signals that are often associated with reward-mediated learning.
Lipid-dependence of target membrane stability during influenza viral fusion
Authors: Haldar Sourav , Mekhedov Elena , McCormick Chad D. , Blank Paul S. , Zimmerberg Joshua 
Published: July 2018

ABSTRACT
Although influenza kills about a half million people each year, even after excluding pandemics, there is only one set of antiviral drugs: neuraminidase inhibitors. By using a new approach utilizing giant unilamellar vesicles and infectious X-31 influenza virus, and testing for the newly identified pore intermediate of membrane fusion, we observed ∼30–87% poration, depending upon lipid composition. Testing the hypothesis that spontaneous curvature (SC) of the lipid monolayer controls membrane poration, our Poisson model and Boltzmann energetic considerations suggest a transition from a leaky to a non-leaky fusion pathway depending on the SC of the target membrane. When the target membrane SC is below approximately −0.20 nm−1 fusion between influenza virus and target membrane is predominantly non-leaky while above that fusion is predominantly leaky, suggesting that influenza hemagglutinin (HA)-catalyzed topological conversion of target membranes during fusion is associated with a loss of membrane integrity.
Why do models of insect respiratory patterns fail?
Authors: Terblanche John S. , Woods H. Arthur 
Published: July 2018

ABSTRACTInsects exchange respiratory gases using an astonishing diversity of patterns. Of these, discontinuous gas exchange cycles (DGCs) have received the most study, but there are many other patterns exhibited intraspecifically and interspecifically. Moreover, some individual insects transition between patterns based on poorly understood combinations of internal and external factors. Why have biologists failed, so far, to develop a framework capable of explaining this diversity? Here, we propose two answers. The first is that the framework will have to be simultaneously general and highly detailed. It should describe, in a universal way, the physical and chemical processes that any insect uses to exchange gases through the respiratory system (i.e. tracheal tubes and spiracles) while simultaneously containing enough morphological, physiological and neural detail that it captures the specifics of patterns exhibited by any species or individual. The second difficulty is that the framework will have to provide ultimate, evolutionary explanations for why patterns vary within and among insects as well as proximate physiological explanations for how different parts of the respiratory system are modified to produce that diversity. Although biologists have made significant progress on all of these problems individually, there has been little integration among approaches. We propose that renewed efforts be undertaken to integrate across levels and approaches with the goal of developing a new class of general, flexible models capable of explaining a greater fraction of the observed diversity of respiratory patterns.
Upper thermal limits of growth in brook trout and their relationship to stress physiology
Authors: Chadwick Joseph G. , McCormick Stephen D. 
Published: July 2018

ABSTRACTDespite the threat of climate change, the physiological mechanisms responsible for reduced performance at high temperatures remain unclear for most species. Elevated but sublethal temperatures may act via endocrine and cellular stress responses to limit performance in important life-history traits such as growth. Here, brook trout (Salvelinus fontinalis) subjected to chronically elevated or daily oscillating temperatures were monitored for growth and physiological stress responses. Growth rate decreased at temperatures above 16°C and was negative at 24°C, with an estimated upper limit for positive growth of 23.4°C. Plasma cortisol increased with temperature and was 12- and 18-fold higher at 22 and 24°C, respectively, than at 16°C, whereas plasma glucose was unaffected by temperature. Abundance of heat shock protein 70 (HSP70) in the gill increased with temperature and was 11- and 56-fold higher at 22°C and 24°C, respectively, than at 16°C. There was no relationship between temperature and plasma Cl−, but there was a 53% and 80% decrease in gill Na+/K+-ATPase activity and abundance at 24°C in comparison with 16°C. Daily temperature oscillations of 4°C or 8°C (19–23°C or 17–25°C) were compared with 21°C controls. Growth rate decreased with temperature and was 43% and 35% lower by length and mass, respectively, in the 8°C daily oscillation treatment than in the controls. There was no effect of temperature oscillation on plasma cortisol or glucose levels. In contrast, gill HSP70 abundance increased with increasing daily oscillation and was 40- and 700-fold greater at 4°C and 8°C daily oscillation, respectively, than in the constant temperature controls. In individuals exposed to 17–25°C diel oscillations for 4 days and then allowed to recover at 21°C, gill HSP70 abundance was still elevated after 4 days recovery, but not after 10 days. Our results demonstrate that elevated temperatures induce cellular and endocrine stress responses and provide a possible mechanism by which growth is limited at elevated temperatures. Temperature limitations on growth may play a role in driving brook trout distributions in the wild.
Silica-induced fibrosis: an ancient response from the early metazoans
Authors: Pozzolini Marina , Scarfì Sonia , Gallus Lorenzo , Ferrando Sara , Cerrano Carlo , Giovine Marco 
Published: July 2018

ABSTRACT
Exposure to crystalline silica particles causes silicosis, an occupational disease leading to an overproduction of collagen in the lung. The first step of this pathology is characterized by the release of inflammatory mediators. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine directly involved in silica-induced pulmonary fibrosis. The marine demosponge Chondrosia reniformis is able to incorporate silica grains and partially dissolve the crystalline forms apparently without toxic effects. In the present work, C. reniformis tissue explants were treated with fine quartz dust and the expression level of fibrogenic genes was assayed by qPCR, demonstrating an overexpression of a fibrillar and a non-fibrillar collagen and of prolyl-4-hydroxylase enzyme. The deposition of new collagen could also be documented in quartz-treated sponge explants. Furthermore, TNF pro-inflammatory cytokine overexpression and involvement in silica-induced sponge collagen biosynthesis was demonstrated in quartz-treated explants as compared with controls by means of specific TNF inhibitors affecting the fibrogenic gene response. As no documentable detrimental effect was observed in treated explants, we conclude that the C. reniformis unique quartz engulfment and erosion is physiological and beneficial to the animal, leading to new collagen synthesis and strengthening of the body stiffness. Thus, we put forward the hypothesis that an ancient physiological behaviour from the lowest of the Metazoa, persisting through evolution via the same molecular mediators such as TNF, may have become the cause of disease in the specialized tissues of higher animals such as mammals.
Hibiscus sabdariffa L.: ESTABILIDADE DA ATIVIDADE ANTIOXIDANTE E CONSTITUINTES QUÍMICOS APÓS PREPARO DO CHÁ
Authors: Martins Ribeiro Andressa Ândria , Martins Diegue Henrique Nascimento , Cibin Gabriela Roso , Silveira Damaris , Magalhães Pérola de Oliveira , Fonseca-Bazzo Yris Maria 
Published: July 2018

A espécie vegetal Hibiscus sabdariffa L. é utilizada devido ao seu gosto peculiar e suas propriedades curativas. A literatura relata propriedades antioxidante, anti-inflamatória e antidiabética para esta planta. Sua utilização é por meio do chá, obtido da infusão de partes da planta, precisamente seu cálice seco. Devido a suas propriedades, o consumodeste chá no Brasil vem crescendo. A avaliação da qualidade é importante de forma a garantir à população a eficácia e segurança de tais produtos. Neste estudo, três marcas de chás de H. sabdariffa L. foram avaliadas quanto a suas propriedades antioxidantes, assim como seu perfil fitoquímico por CLAE/DAD. Foram utilizados os métodos deperoxidação lipídica e inibição da formação do complexo fosfomolibdênio para a avaliação da atividade antioxidante. Para melhor orientação do consumo deste chá, foi avaliada a estabilidade da atividade antioxidante após 1 e 12 horas do preparo. Na análise cromatográfica foi detectada a presença de ácido neoclorogênico para as três marcas avaliadas. Os chás apresentaram atividade antioxidante nos dois métodos avaliados. Contudo, a atividade antioxidante tende a reduzir após 12 horas. Esta tendência à redução de atividade possibilita a orientação para o consumo do chá de H. sabdariffa L. até 12 horas após preparo.
The Impact of Customer Relationship Management on Tourist Satisfaction: The Case of Radisson Blue Resort in Aqaba City
Authors: ALANANZEH Omar Abedalla , MASA'DEH Ra'ed , JAWABREH Omar , MAHMOUD Ali Al , HAMADA Randa 
Published: July 2018

Aims: This paper aims at investigating the effects of customer relationship management in terms of tourist attractions and facilities, outlets (F&B), and front office services on tourist satisfaction.
Design: A total of 136 questionnaires containing 34 items was used to collect information from tourists in Radisson resort in Aqaba city located in Jordan. Multiple regression analysis was conducted to test the research hypotheses.
Findings: Results of the current study revealed that there is a significant impact of tourist attractions and facilities, and front office services on tourist satisfaction, whereas outlets (F&B), has no significant impact on it. Results of T-test showed that there is no significant difference in the impact of tourist satisfaction that in favor of gender. Also, results of ANOVA test indicated that there is no significant difference in the impact of tourist satisfaction that can be attributed to age, occupation, educational level, the purpose of the visit, holiday booked a date and a number of previous visits.
Implications: this study will contribute a better understanding of tourist’s satisfaction through proper customer relationship management in terms of tourist facilities, outlets, and front office services.
Originality: This study is considered the first case study that links tourist satisfaction with the prober management of the hotel facilities and outlets
Batur toward Sustainable Tourism Development - A Community-based Geotourism Case from Bali in Indonesia
Authors: ERNAWATI Ni Made , SITAWAT Anak Agung Raka , MULIATI Ni Kadek 
Published: July 2018

This paper discusses contemporary issues in developing Batur toward a sustainable geotourism site. It is a result of a qualitative study using a combined method of document review, observation and direct participation as data collecting methods. Natural conservation is one of the vocal points of Batur geotourism, as it uses natural environment as attraction and venue. Tourism brings benefits to people in Batur who used to have farming as the only major occupation; since tourism was introduced in this area people’s profession diversified. In general, the benefits of tourism reasonably reinforce a better living in Batur, these such as better economic, infrastructure and landscaping; more appreciation and attention to natural environment and culture; broader social interaction and wider perspective and horizon of the people. Nonetheless, more efforts need to be exerted for better tourism development results. Currently, Batur tourism management operates in fractions, to maximize the benefits from tourism, a systematic and integrated management needs to be devised with the collaboration of stakeholders that enables the provision of quality tourism products and services, an integrated promotion, the availability of tourism facilities and infrastructure that harmoniously coexist with nature, the establishment of network, and the application of regulations that support sustainable tourism.
Study of Complications of Varicella-Zoster Virus Infection in Hospitalized Children at a Reference Hospital for Infectious Disease Treatment
Authors: Diniz Lilian Martins Oliveira , Maia Marcelle Marie Martins , Oliveira Yara Vieira de , Mourão Marina Santos Falci , Couto Amanda Vieira , Mota Vânia Carneiro , Versiani Carolina Mazieiro , Silveira Priscila Olívia da Costa , Romanelli Roberta Maia Castro 
Published: July 2018

OBJECTIVES:Varicella is a disease with potentially severe complications. We aimed to investigate characteristics of hospitalized children with varicella in Brazil in the prevaccine period and to identify predictors for requiring intensive care treatment.METHODS:A prospective cohort study was conducted from May 2011 to April 2014. Patients up to 13 years of age with varicella diagnosis were included. Information was collected through interview and review of medical records. Logistic regression analysis was performed.RESULTS:A total of 669 patients were admitted. The median age of subjects was 2.7 years (range 0–14 years) with a predominance of boys (56.6%). The main causes of hospitalization were bacterial complications (77.7%), viral complications (11.4%), and at-risk patients (10.9%). Main bacterial complications were skin infection and pneumonia. Main viral complications were herpes zoster, cerebellitis, and encephalitis. Most at-risk patients used corticosteroids or had a diagnosis of leukemia. At-risk patients were hospitalized earlier (P &lt; .01) and remained hospitalized for longer periods (P = .03). A total of 44 patients (6.6%) were admitted to the ICU, and 5 (0.8%) died of septic shock. Thrombocytopenia was associated with more severe illness in patients with bacterial infections (P = .001). The long-time interval between onset of infection and admission was associated with the need for intensive care in all groups (P = .007).CONCLUSIONS:Secondary bacterial infection is the main cause of hospitalization, and thrombocytopenia in these patients leads to worse outcomes. Difficulties of access to the health system and delay in medical care are determining factors of greater severity in this population.
TECHNOLOGY OF PRODUCING SYMBIOTIC BIOLOGICALLY ACTIVE ADDITIVE
Authors: Krupytska L. , Kaprelyants L. , Trufkati L. , Velichko T. , Kirilov V. 
Published: July 2018

The article presents data on the development of the technology of multicomponent probiotics from two bacterial strains: Bifidobacterium longum-Ya3 and Propionibacterium shermanii-4. The ability of bacteria of the genus Propionibacterium to have a selective stimulating effect on the growth of bacteria of the genus Bifidobacterium has been characterised. Based on the experimental data obtained with the MATLAB software, optimal conditions were determined for the accumulation of the maximum amount of biomass of the consortium of Bifidobacterium longum-Ya3 and Propionibacterium shermanii-4. The main parameters that determined the yield of biomass in the process of cultivation under different temperature conditions (T=30°С, Т=34 °С, Т=37 °С) have been taken as the optimality criteria. These parameters are the number of colony-forming units and the active acidity. It has been established that the optimal time for cultivating a consortium of bifidobacteria and propionibacteria in a soy-lactose medium is 24 hours at a temperature of 34°C. On the basis of the data obtained, we have created a symbiotic BAA (biologically active additive) and developed a basic technological scheme for its production. The biologically active additive was created on the basis of the symbiotic consortium of bifido and propionibacteria containing 4 × 1010 CFU/cm3 of B. longum-Ya3, and 3 × 1010 CFU/cm3 of P. shermanii-4. The microbiological control of the quality of the obtained dietary supplement based on the consortium of the bacteria Bifidobacterium longum-Ya3 and Propionibacterium shermanii-4 has found no pathogenic and sanitary indicator microorganisms. It means that the finished product is safe and suitable for consumption. As for the organoleptic parameters, the BAA obtained is of a powder-like structure, beige-coloured, with a specific taste and smell.