Benzothiadiazole-based rotation and possible antipolar order in carboxylate-based metal-organic frameworks

By modifying organic ligands of metal-organic framework with dipolar units, they turn suitable for various applications, e.g., in the field of sensor systems or switching of gas permeation. Dipolar linkers in the organic ligand are capable to rotate in certain temperature and frequency ranges. The copper-bearing paddlewheel shaped metal-organic frameworks ZJNU-40 and JLU-Liu30 possess such a polarizable dipole moment due to their benzothiadiazole moiety in the organic ligands. Here, we investigate the molecular rotor behavior of benzothiadiazole units of the two carboxylate-based MOFs by dielectric spectroscopy and computational simulation. Our dielectric results provide clear evidence for significant reorientational relaxation dynamics of these rotors, revealing various characteristics of glasslike freezing upon cooling. The calculated rotational energy barriers are consistent with experimentally determined barriers for single-dipole dynamics. Moreover, for JLU-Liu30 we find hints at antipolar ordering below about 300 K

Translational and reorientational dynamics in carboxylic acid-based deep eutectic solvents

The glass formation and the dipolar reorientational motions in deep eutectic solvents (DESs) are frequently overlooked, despite their crucial role in defining the room-temperature physiochemical properties. To understand the effects of these dynamics on the ionic conductivity and their relation to the mechanical properties of the DES, we conducted broadband dielectric and rheological spectroscopy over a wide temperature range on three well-established carboxylic-acid-based natural DESs: These are the eutectic mixtures of choline chloride with oxalic acid (oxaline), malonic acid (maline), and phenylacetic acid (phenylaceline). In all three DESs, we observe signs of a glass transition in the temperature dependence of their dipolar reorientational and structural dynamics, as well as varying degrees of motional decoupling between the different observed dynamics: Maline and oxaline display a breaking of the Walden rule near the glass-transition temperature, while the relation between the dc conductivity and dipolar relaxation time in both maline and phenylaceline is best described by a power law. The glass-forming properties of the investigated systems not only govern the orientational dipolar motions and rheological properties, which are of interest from a fundamental point of view, but they also affect the dc conductivity, even at room temperature, which is of high technical relevance

Mapping the Road from Childhood Trauma to Adult Somatization: The Role of Attachment

Objective: This study tested whether insecure attachment mediates the link between childhood trauma and adult somatization. Methods: A community sample of 101 couples completed self-report measures including the Relationship Scales Questionnaire, the Childhood Trauma Questionnaire, the Somatic Symptom Inventory, the Beck Depression Inventory, and the Conflict Tactics Scale. Results: Childhood trauma was associated with higher levels of somatization and insecure attachment. Insecure attachment style was also associated with higher levels of somatization. Controlling for age, income, and recent intimate partner violence, analyses showed that fearful attachment fully mediated the link between childhood trauma and somatization for women. For men there was no such mediation, but both childhood trauma and insecure attachment styles made independent contributions to predicting levels of somatization. Conclusions: Findings are consistent with the hypothesis that, for women, childhood trauma influences adult levels of somatization by fostering insecure adult attachment. For men, findings suggest that trauma and attachment are both important independent predictors of adult somatization. Study results support the idea that childhood trauma shapes patients’ styles of relating to others in times of need and these styles in turn influence the somatization process and how patients respond to providers. Screening for attachment style may provide information that could allow health care providers to tailor treatment more effectively. Key words: Attachment style, somatization, childhood trauma, interpersonal models. Abbreviations: CTQ = Childhood Trauma Questionnaire; CTS2 = Conflict Tactics Scale version 2; SSI = Somatic Symptom Inventory; RSQ = Relationship Scales Questionnaire; BDI = Beck Depression Inventory

Mapping the Road from Childhood Trauma to Adult Somatization: The Role of Attachment

Objective: This study tested whether insecure attachment mediates the link between childhood trauma and adult somatization. Methods: A community sample of 101 couples completed self-report measures including the Relationship Scales Questionnaire, the Childhood Trauma Questionnaire, the Somatic Symptom Inventory, the Beck Depression Inventory, and the Conflict Tactics Scale. Results: Childhood trauma was associated with higher levels of somatization and insecure attachment. Insecure attachment style was also associated with higher levels of somatization. Controlling for age, income, and recent intimate partner violence, analyses showed that fearful attachment fully mediated the link between childhood trauma and somatization for women. For men there was no such mediation, but both childhood trauma and insecure attachment styles made independent contributions to predicting levels of somatization. Conclusions: Findings are consistent with the hypothesis that, for women, childhood trauma influences adult levels of somatization by fostering insecure adult attachment. For men, findings suggest that trauma and attachment are both important independent predictors of adult somatization. Study results support the idea that childhood trauma shapes patients’ styles of relating to others in times of need and these styles in turn influence the somatization process and how patients respond to providers. Screening for attachment style may provide information that could allow health care providers to tailor treatment more effectively. Key words: Attachment style, somatization, childhood trauma, interpersonal models. Abbreviations: CTQ = Childhood Trauma Questionnaire; CTS2 = Conflict Tactics Scale version 2; SSI = Somatic Symptom Inventory; RSQ = Relationship Scales Questionnaire; BDI = Beck Depression Inventory

On-line Sensor Control for Milk Powder and Cheese Manufacture.

End of Project ReportThis project investigated the use of on-line sensors of rheological characteristics which can be measured during the manufacture of milk powder and cheese. The objective is to use on-line measurements to fine tune each process, so as to compensate for the variability of milk.Department of Agriculture, Food and the Marin

Transformação hidrotérmica do glicerol a ácido lático em meio alcalino utilizando catalisadores de Cu obtidos a partir de precursores do tipo-hidrotalcita

A perspectiva de diminuição de emissões de carbono na atmosfera tem motivado o desenvolvimento e utilização de combustíveis renováveis. Neste contexto, verifica-se crescimento na produção e comercialização do biodiesel nos últimos anos. Uma grande quantidade de glicerol bruto tem sido gerada como subproduto, criando um enorme excedente no mercado, e transformando-o em passivo ambiental. Verifica-se uma vasta gama de trabalhos científicos que buscam o reaproveitamento deste glicerol, com a conversão a produtos de maior valor agregado. Em destaque, citamos o ácido lático, que apresenta aplicação nas indústrias química, farmacêutica e alimentícia. A produção de ácido lático a partir do glicerol, em meio alcalino, via rota catalítica vem ganhando espaço e tem se mostrado uma alternativa eficiente frente a rota convencional fermentativa. Neste trabalho investigou-se a produção de ácido lático a partir do glicerol, em meio alcalino, utilizando catalisadores de cobre obtidos a partir de precursores do tipo-hidrotalcita em sistema reacional de fluxo contínuo, bem como o efeito de diferentes concentrações de cobre e a estabilidade dos catalisadores frente ao rendimento e a seletividade a ácido lático. Os catalisadores foram preparados pelo método de coprecipitação e caracterizados por fluorescência de raios X (FRX), difração de raios X (DRX), propriedades texturais, redução à temperatura programada (TPR) e dessorção de CO2 à temperatura programada (TPD-CO2) e a dispersão de cobre foi determinada por oxidação por N2O. Os testes catalíticos foram realizados a 240 °C, 35 atm, velocidade espacial (WHSV) de 2 h-1, solução de glicerol 10% v/v e razão molar NaOH/glicerol de 0,75 durante 30h. Embora o catalisador 30CuHT tenha apresentado propriedades catalítlicas levemente superiores ao catalisador 20CuHT, os melhores resultados em termos de conversão do glicerol (96,5%) e rendimento (64 %) a ácido lático foram obtidos no teste catalítico executado com o catalisador 20CuHT. Resultado que pode estar relacionado à influência das reações que ocorrem com as hidroxilas na fase líquida, as quais não possuem uma dependência direta com o catalisador. Por fim, observou-se que os catalisadores exibiram estabilidade catalítica, sem evidências de desativação durante o período avaliado

Intestinal GUCY2C prevents TGF-β secretion coordinating desmoplasia and hyperproliferation in colorectal cancer.

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to secrete hepatocyte growth factor (HGF), reciprocally driving colon cancer cell proliferation through cMET-dependent signaling. Elimination of GUCY2C signaling in mice (Gucy2c(-/-)) produces intestinal desmoplasia, with increased reactive myofibroblasts, which is suppressed by anti-TGF-β antibodies or genetic silencing of Akt. Thus, GUCY2C coordinates intestinal epithelial-mesenchymal homeostasis through reciprocal paracrine circuits mediated by TGF-β and HGF. In that context, GUCY2C signaling constitutes a direct link between the initiation of colorectal cancer and the induction of its associated desmoplastic stromal niche. The recent regulatory approval of oral GUCY2C ligands to treat chronic gastrointestinal disorders underscores the potential therapeutic opportunity for oral GUCY2C hormone replacement to prevent remodeling of the microenvironment essential for colorectal tumorigenesis

General Practice Management of Type 2 Diabetes: 2016–18

[Extract] Diabetes is a national health priority. The Australian National Diabetes Strategy 2016–2020was released by the Australian Government in November 2013. The number of people with type 2 diabetes is growing, most likely the result of rising overweight and obesity rates, lifestyle and dietary changes, and an ageing population. Within 20 years, the number of people in Australia with type 2 diabetes may increase from an estimated 870,000 in 2014, to more than 2.5 million.1The most socially disadvantaged Australians are twice as likely to develop diabetes. If left undiagnosed or poorly managed, type 2 diabetes can lead to coronary artery disease (CAD), stroke, kidney failure, limb amputations and blindness. The early identification and optimal management of people with type 2 diabetes is therefore critical. General practice has the central role in type 2 diabetes management across the spectrum, from identifying those at risk right through to caring for patients at the end of life. These guidelines give up-to-date, evidence-based information tailored for general practice to support general practitioners (GPs) and their teams in providing high-quality management.1In the development of the 2016–18 edition of General practice management of type 2 diabetes, The Royal Australian College of General Practitioners (RACGP) has focused on factors relevant to current Australian clinical practice. The RACGP has used the skills and knowledge of your general practice peers who have an interest in diabetes management and are members of the RACGP Specific Interests Diabetes Network. This publication has been produced in accordance with the rules and processes outlined in the RACGP’s conflict of interest (COI) policy. The RACGP’s COI policy is available at www.racgp.org.au/support/policies/organisationalThis edition represents 19 years of a successful relationship between the RACGP and Diabetes Australia. We acknowledge the support of the RACGP Expert Committee – Quality Care, the Medical Education and Scientific Committee of Diabetes Australia, and RACGP staff in the development of these guideline

Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells

Background Detection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection. Methods HER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT-PCR, western blot and fluorescence-activated cell scanning (FACS) and compared to the strongly HER2-expressing breast cancer cell line SKBR3 and other controls. HER2 expression in UC patient tissues was measured by qRT PCR and correlated with data on survival and risk for metastasis. UCCs with high EpCAM and variable HER2 expression were used for spike-in experiments in the CellSearch system. Twenty-one blood samples from 13 metastatic UC patients were analyzed for HER2-positive CTCs with CellSearch. Results HER2 mRNA and protein were broadly expressed in UCC, with some heterogeneity, but at least 10-fold lower than in the HER-2+ SKBR3 cells. Variations were unrelated to cellular phenotype or clinicopathological characteristics. EpCAM expression was essentially restricted to UCCs with epitheloid phenotypes. Heterogeneity of EpCAM and HER2 expression was observed also in spike-in experiments. The 7 of 21 blood samples from 6 of 13 patients were enumerated as CTC positive via EpCAM, but only one sample stained weakly positive (1+) for HER2. Conclusions Detection rate of CTCs by EpCAM in UC is poor, even in metastatic patients. Because of its widespread expression, particularly in patients with high risk of metastasis, detection of HER2 could improve identification of UC CTCs, which is why combined detection using antibodies for EpCAM and HER2 may be beneficial

Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity

Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair. We find that loss of Merlin in these cells causes a catastrophic failure of axonal regeneration and remyelination in the PNS. This effect is mediated by activation of YAP expression in Merlin-null SCs, and loss of YAP restores axonal regrowth and functional repair. This work identifies new mechanisms that control the regenerative potential of SCs and gives new insight into understanding the correct control of functional nerve repair in the PNS