A high yield (>36 wt %) method has been developed of preparing monolayered tungsten dichalcogenide (WS2) quantum dots (QDs) with lateral size ∼8-15 nm from multilayered WS2 flakes. The monolayered WS2 QDs are, like monolayered WS2 sheets, direct semiconductors despite the flake precursors being an indirect semiconductor. However, the QDs have a significantly larger direct transition energy (3.16 eV) compared to the sheets (2.1 eV) and enhanced photoluminescence (PL; quantum yield ∼4%) in the blue-green spectral region at room temperature. UV/vis measurements reveal a giant spin-valley coupling of the monolayered WS2 QDs at around 570 meV, which is larger than that of monolayered WS2 sheets (∼400 meV). This spin-valley coupling was further confirmed by PL as direct transitions from the conduction band minimum to split valence band energy levels, leading to multiple luminescence peaks centered at around 369 (3.36 eV) and 461 nm (2.69 eV, also contributed by a new defect level). The discovery of giant spin-valley coupling and the strong luminescence of the monolayered WS2 QDs make them potentially of interests for the applications in semiconductor-based spintronics, conceptual valley-based electronics, quantum information technology and optoelectronic devices. However, we also demonstrate that the fabricated monolayered WS2 QDs can be a nontoxic fluorescent label for high contrast bioimaging application.

Monolayered boron nitride (BN) quantum dots (QDs; lateral size ≈10 nm) are fabricated using a novel method. Unlike monolayered BN sheets, these BN QDs exhibit blue-green luminescence due to defects formed during preparation. This optical behavior adds significant functionality to a material that is already receiving much attention. It is further shown that the QDs are nontoxic to biological cells and well suited to bio-imaging.

Autosomal-dominant polycystic kidney disease (ADPKD) is one of the most common human monogenic diseases with an incidence of 1:400 to 1:1000. It is characterized by the progressive development and enlargement of focal cysts in both kidneys, typically resulting in end-stage renal disease (ESRD) by the fifth decade. The cystogenic process is highly complex with a cellular phenotype consistent with "dedifferentiation" (i.e., a high proliferative rate, increased apoptosis, altered protein sorting, changed secretory characteristics, and disorganization of the extracellular matrix). Although cystic renal disease is the major cause of morbidity, the occurrence of nonrenal cysts, most notably in the liver (occasionally resulting in clinically significant polycystic liver disease) and the increased prevalence of other abnormalities including intracranial aneurysms, indicate that ADPKD is a systemic disorder. Following the identification of the first ADPKD gene, PKD1, 10 years ago and PKD2 2 years later, considerable progress has been made in defining the etiology and understanding the pathogenesis of this disorder, knowledge that is now leading to the development of several promising new therapies. The purpose of this review is to summarize our current state of knowledge as to the structure and function of the PKD1 and PKD2 proteins, polycystin-1 and -2, respectively, and explore how mutation at these loci results in the spectrum of changes seen in ADPKD.

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The functions of the two proteins defective in autosomal dominant polycystic kidney disease, polycystin-1 and polycystin-2, have not been fully clarified, but it has been hypothesized that they may heterodimerize to form a "polycystin complex" involved in cell adhesion. In this paper, we demonstrate for the first time the existence of a native polycystin complex in mouse kidney tubular cells transgenic for PKD1, non-transgenic kidney cells, and normal adult human kidney. Polycystin-1 is heavily N-glycosylated, and several glycosylated forms of polycystin-1 differing in their sensitivity to endoglycosidase H (Endo H) were found; in contrast, native polycystin-2 was fully Endo H-sensitive. Using highly specific antibodies to both proteins, we show that polycystin-2 associates selectively with two species of full-length polycystin-1, one Endo H-sensitive and the other Endo H-resistant; importantly, the latter could be further enriched in plasma membrane fractions and coimmunoprecipitated with polycystin-2. Finally, a subpopulation of this complex co-localized to the lateral cell borders of PKD1 transgenic kidney cells. These results demonstrate that polycystin-1 and polycystin-2 interact in vivo to form a stable heterodimeric complex and suggest that disruption of this complex is likely to be of primary relevance to the pathogenesis of cyst formation in autosomal dominant polycystic kidney disease.

Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1–3 at initiation of treatment with evidence of rapidly progressing disease. In this paper, on behalf of the ERA-EDTA Working Groups of Inherited Kidney Disorders and European Renal Best Practice, we aim to provide guidance for making the decision as to which ADPKD patients to treat with tolvaptan. The present position statement includes a series of recommendations resulting in a hierarchical decision algorithm that encompasses a sequence of risk-factor assessments in a descending order of reliability. By examining the best-validated markers first, we aim to identify ADPKD patients who have documented rapid disease progression or are likely to have rapid disease progression. We believe that this procedure offers the best opportunity to select patients who are most likely to benefit from tolvaptan, thus improving the benefit-to-risk ratio and cost-effectiveness of this treatment. It is important to emphasize that the decision to initiate treatment requires the consideration of many factors besides eligibility, such as contraindications, potential adverse events, as well as patient motivation and lifestyle factors, and requires shared decision-making with the patient.

Polycystic kidney disease 1 (PKDI) is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease. We have studied PKDI mRNA, with an RNase protection assay, and found widespread expression in adult tissue, with high levels in brain and moderate signal in kidney. Expression of the PKD1 protein, polycystin, was assessed in kidney using monoclonal antibodies to a recombinant protein containing the C terminus of the molecule. In fetal and adult kidney, staining is restricted to epithelial cells. Expression in the developing nephron is most prominent in mature tubules, with lesser staining in Bowman's capsule and the proximal ureteric bud. In the nephrogenic zone, detectable signal was observed in comma-and S-shaped bodies as well as the distal branches of the ureteric bud. By contrast, uninduced mesenchyme and glomerular tufts showed no staining. In later fetal (>20 weeks) and adult kidney, strong staining persists in cortical tubules with moderate staining detected in the loops of Henle and collecting ducts. These results suggest that polycystin's major role is in the maintenance of renal epithelial differentiation and organization from early fetal life. Interestingly, polycystin expression, monitored at the mRNA level and by immunohistochemistry, appears higher in cystic epithelia, indicating that the disease does not result from complete loss of the protein.

A second gene for autosomal dominant polycystic kidney disease (ADPKD) , PKD2, has been recently identified. Using antisera raised to the human PKD2 protein , polycystin-2 , we describe for the first time its distribution in human fetal tissues , as well as its expression in adult kidney and polycystic PKD2 tissues. Its expression pattern is correlated with that of the PKD1 protein , polycystin-1. In normal kidney, expression of polycystin-2 strikingly parallels that of polycystin-1 , with prominent expression by maturing proximal and distal tubules during development, but with a more pronounced distal pattern in adult life. In nonrenal tissues expression of both polycystin molecules is identical and especially notable in the developing epithelial structures of the pancreas, liver , lung , bowel , brain , reproductive organs, placenta , and thymus. Of interest , nonepithelial cell types such as vascular smooth muscle , skeletal muscle , myocardial cells , and neurons also express both proteins. In PKD2 cystic kidney and liver , we find polycystin-2 expression in the majority of cysts, although a significant minority are negative , a pattern mirrored by the PKD1 protein. The continued expression of polycystin-2 in PKD2 cysts is similar to that seen by polycystin-1 in PKD1 cysts , but contrasts with the reported absence of polycystin-2 expression in the renal cysts of Pkd2؉/؊ mice. These results suggest that if a two-hit mechanism is required for cyst formation in PKD2 there is a high rate of somatic missense mutation. The coordinate presence or loss of both polycystin molecules in the same cysts supports previous experimental evidence that hetero- Renal cysts are the primary cause of morbidity in autosomal dominant polycystic kidney disease (ADPKD) but it is evident that the disease phenotype extends beyond the kidney. Cysts are commonly found in the liver and pancreas and have been reported in testis, spleen, ovary, uterus, esophagus, and brain. Moreover, abnormalities suggestive of a generalized disorder of connective tissue, including cardiac valvular abnormalities (especially mitral valve prolapse), intracranial berry aneurysms, colonic diverticulae, inguinal hernia, and a family with Marfanoid habitus, have been described. 1,2 Mutations in two genes, PKD1 and PKD2, account for the vast majority of patients with ADPKD. The identification of these genes 3,4 has thus provided a new opportunity to study the pathophysiology of ADPKD. The predicted proteins appear quite different in structure (the PKD1 protein, polycystin-1, is ϳ4 times larger than its counterpart, polycystin-2 4,5 ). Nonetheless, they share a significant region of homology in their transmembrane regions, an area also similar to a family of voltage-gated calcium/sodium channels. 4,6 Recent evidence indicates that the ADPKD proteins may interact in experimental systems. 7,8 PKD2 is less prevalent than PKD1, accounting for ϳ15% of ADPKD cases, 9,10 but preliminary evidence suggests they share the same spectrum of extrarenal manifestations. In one st...