Astrupiversen1658

Kidney stone disease (nephrolithiasis) is a common problem that can be associated with alterations in urinary solute composition including hypercalciuria. Studies suggest that the prevalence of monogenic kidney stone disorders, including renal tubular acidosis with deafness, Bartter syndrome, primary hyperoxaluria and cystinuria, in patients attending kidney stone clinics is ∼15%. However, for the majority of individuals, nephrolithiasis has a multifactorial aetiology involving genetic and environmental factors. Nonetheless, the genetic influence on stone formation in these idiopathic stone formers remains considerable and twin studies estimate a heritability of >45% for nephrolithiasis and >50% for hypercalciuria. The contribution of polygenic influences from multiple loci have been investigated by genome-wide association and candidate gene studies, which indicate that a number of genes and molecular pathways contribute to the risk of stone formation. Genetic approaches, studying both monogenic and polygenic factors in nephrolithiasis, have revealed that the following have important roles in the aetiology of kidney stones transporters and channels; ions, protons and amino acids; the calcium-sensing receptor (a G protein-coupled receptor) signalling pathway; and the metabolic pathways for vitamin D, oxalate, cysteine, purines and uric acid. These advances, which have increased our understanding of the pathogenesis of nephrolithiasis, will hopefully facilitate the future development of targeted therapies for precision medicine approaches in patients with nephrolithiasis.Background The incidence of cervical cancer in young women is rising, and squamous cell carcinoma makes up a great percentage of the histological types. The presence of aggressive pathologic risk factors following patients' primary surgery may warrant the use of adjuvant radiotherapy. It is important to weigh up the risks and benefits of using adjuvant radiotherapy for each young patient so as to maximize their prognosis while minimizing the treatment-related morbidity. Methods A retrospective study was performed. It consisted of 97 patients under 35 years old who were diagnosed with cervical squamous cell carcinoma and underwent treatment at West China Second University Hospital between December 2009 and January 2014. Five-year follow-up, prognostic risks, long-term radiation toxicity, female sexual function, and quality of life were investigated. Results Adjuvant radiotherapy did improve the prognosis of young patients with lymph node metastases. However, there were few significant differences in progress-free survival and overall survival for the young patients without lymph node metastases following adjuvant radiotherapy. Besides, young patients who took radiotherapy exhibited greater intestinal dysfunction, more severe lower extremities edema, greater sexual dysfunction, and worse long-term quality of life. Conclusion Young patients with early-stage cervical squamous cell carcinoma without lymph node metastases who have undergone the primary surgery should be counseled in detail before the decision to use adjuvant radiotherapy can be made. The counseling should emphasize not only the benefit that local recurrence rates can be reduced, but also the risks that treatment-related side effects could increase and lower QoL could occur.Synthetic membranes with pores at the subnanometre scale are at the core of processes for separating solutes from water, such as water purification and desalination. While these membrane processes have achieved substantial industrial success, the capability of state-of-the-art membranes to selectively separate a single solute from a mixture of solutes is limited. Such high-precision separation would enable fit-for-purpose treatment, improving the sustainability of current water-treatment processes and opening doors for new applications of membrane technologies. Herein, we introduce the challenges of state-of-the-art membranes with subnanometre pores to achieve high selectivity between solutes. We then analyse experimental and theoretical literature to discuss the molecular-level mechanisms that contribute to energy barriers for solute transport through subnanometre pores. We conclude by providing principles and guidelines for designing next-generation single-species selective membranes that are inspired by ion-selective biological channels.ADNP (Activity Dependent Neuroprotective Protein) is a neuroprotective protein whose aberrant expression has been frequently linked to neural developmental disorders, including the Helsmoortel-Van der Aa syndrome (also called the ADNP syndrome). However, its role in neural development and pathology remains unclear. Here, we show that ADNP is required for neural induction and differentiation by enhancing Wnt signaling. Mechanistically, ADNP functions to stabilize β-Catenin through binding to its armadillo domain which prevents its association with key components of the degradation complex Axin and APC. selleck chemical Loss of ADNP promotes the formation of the degradation complex and β-Catenin degradation via ubiquitin-proteasome pathway, resulting in down-regulation of key neuroectoderm developmental genes. In addition, adnp gene disruption in zebrafish leads to defective neurogenesis and reduced Wnt signaling. Our work provides important insights into the role of ADNP in neural development and the pathology of the Helsmoortel-Van der Aa syndrome caused by ADNP gene mutation.The experience of motherhood is one of the most salient events in a woman's life. Motherhood is associated with a series of neurophysiological, psychological, and behavioral changes that allow women to better adapt to their new role as mothers. Infants communicate their needs and physiological states mainly through salient emotional expressions, and maternal responses to infant signals are critical for infant survival and development. In this study, we investigated the whole brain functional response to emotional infant faces in 20 new mothers and 22 nulliparous women during functional magnetic resonance imaging scans. New mothers showed higher brain activation in regions involved in infant facial expression processing and empathic and mentalizing networks than nulliparous women. Furthermore, magnitudes of the activation of the left parahippocampal gyrus and the left fusiform gyrus, recruited during facial expression processing, were positively correlated with empathic concern (EC) scores in new mothers when viewing emotional (happy-sad) faces contrasted to neutral faces.