New Insight into the Fluorescence Quenching of Nitrogen-Containing Carbonaceous Quantum Dots—From Surface Chemistry to Biomedical Applications

Carbon-based quantum dots are widely suggested as fluorescent carriers of drugs, genes or other bioactive molecules. In this work, we thoroughly examine the easy-to-obtain, biocompatible, nitrogen-containing carbonaceous quantum dots (N-CQDs) with stable fluorescent properties that are resistant to wide-range pH changes. Moreover, we explain the mechanism of fluorescence quenching at extreme pH conditions. Our in vitro results indicate that N-CQDs penetrate the cell membrane; however, fluorescence intensity measured inside the cells was lower than expected from carbonaceous dots extracellular concentration decrease. We studied the mechanism of quenching and identified reduced form of β-nicotinamide adenine dinucleotide (NADH) as one of the intracellular quenchers. We proved it experimentally that the elucidated redox process triggers the efficient reduction of amide functionalities to non-fluorescent amines on carbonaceous dots surface. We determined the 5 nm–wide reactive redox zone around the N-CQD surface. The better understanding of fluorescence quenching will help to accurately quantify and dose the internalized carbonaceous quantum dots for biomedical applications.     

Glycine‐modified growth hormone secretagogues identified in seized doping material

A number of unknown pharmaceutical preparations seized by Danish customs authorities were submitted for liquid chromatography–high resolution mass spectrometry (LC–HRMS) analysis. Comparison with reference standards unequivocally identified the content of the powders as analogs of the growth hormone secretagogues GHRP‐2 (Pralmorelin), GHRP‐6, Ipamorelin, and modified growth hormone releasing factor (modified GRF 1–29), which can be used as performance‐enhancing substances in sports. In all cases, the detected modification involved the addition of an extra glycine amino acid at the N‐terminus, and analytical methods targeting growth hormone secretagogues should hence be updated accordingly.     

Structure and Function of the Armored Keel in Piranhas,Pacus, and their Allies

The serrasalmids: piranhas, pacus, and their relatives, are ubiquitous Neotropical fishes with diverse diets, ecologies, and behaviors. Serrasalmids have a bony, serrated keel which lines the underbellies of these fishes, the structure for which the family is named. We examined the diversity and structure of the keel in piranhas and allies using micro-computed tomography scanning in over 30 species of serrasalmids, a third of the species richness for the family, and for 95 total characiform specimens. The keel is highly diverse across serrasalmids, with serrae shape dictating the overall form of the keel. Serrae shape varies considerably among different species and even within keels themselves. The keel morphology can be divided into distinct anterior and posterior regions, as separated by the pelvic fins. Compared to other characiform fishes, serrasalmid skeletons are frequently damaged. Gouging perforations and signs of healing (serrae fusion) are common on the keel. We propose the keel is a defensive structure based on the high incidence of injury (>50%) in our dataset. This is the highest incidence of damage ever recorded in the skeletons of bony fishes. The loss of the anterior keel region in rheophilic taxa suggests competing performance demands and selective pressures on this structure. Competition and aggression among conspecifics or confamilials is a frequently invoked phenomenon for explaining animal weaponry and armor in terrestrial vertebrates. The keel in serrasalmids and other instances of armor in fishes could be complementary study systems for examining competitive rivalry in vertebrates. Anat Rec, 2018. © 2018 American Association for Anatomy.     

Cognitive and psychiatric symptoms in genetically determined Parkinson’s disease: a systematic review

The aim was to review the existing reports on cognitive and behavioural symptoms in monogenic forms of Parkinson’s disease (PD) and to identify recurring patterns of clinical manifestations in those with specific mutations. A systematic literature search was conducted to retrieve observational studies of monogenic PD. Data pertaining to cognitive and psychiatric manifestations were extracted using standardized templates. The PRISMA guidelines were followed. Of the 1889 citations retrieved, 95 studies on PD‐related gene mutations were included: 35 in SNCA, 35 in LRRK2, four in VPS35, 10 in Parkin, three in DJ1 and eight in PINK1. Nineteen studies (20%) provided adequate data from comprehensive cognitive assessment and 31 studies (32.6%) outlined psychiatric manifestations through the use of neuropsychiatric scales. Cognitive impairment was reported in all monogenic PD forms with variable rates (58.8% PINK1, 53.9% SNCA, 50% DJ1, 29.2% VPS35, 15.7% LRRK2 and 7.4% Parkin). In this regard, executive functions and attention were the domains most affected. With respect to psychiatric symptoms, depression was the most frequent symptom, occurring in 37.5% of PINK1 cases and 41.7% of VPS35 and LRRK2 cases. Co‐occurrence of cognitive decline with visual hallucinations was evidenced. Widespread accumulation of Lewy bodies, distinctive of SNCA, PINK1 and DJ1 mutations, results in higher rates of cognitive impairment. Similarly, a higher degree of visual hallucinations is observed in SNCA mutations, probably owing to the more widespread accumulation. The lower rates of α‐synuclein pathology in LRRK2 and Parkin may underpin the more benign disease course in these patients.     

Nutritional therapy for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and presents together with cirrhosis in most cases. In addition to commonly recognized risk factors for HCC development, such as hepatitis B virus/hepatitis C virus infection, age and alcohol/tobacco consumption, there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat, type of cooking (generation of heterocyclic amines) and contamination of foods with aflatoxins. On the contrary, protective nutritional factors include diets rich in fiber, fruits and vegetables, n-3 polyunsaturated fatty acids and coffee. While the patient is being evaluated for staging and treatment of HCC, special attention should be paid to nutritional support, including proper nutritional assessment and therapy by a multidisciplinary team. It must be considered that these patients usually develop HCC on top of long-lasting cirrhosis, and therefore they could present with severe malnutrition. Cirrhosis-related complications should be properly addressed and considered for nutritional care. In addition to traditional methods, functional testing, phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional assessment. Nutritional therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and cancer. Supplementation with branched-chain amino acids is also recommended as it improves response to treatment, nutritional status and survival, and finally physical exercise must be encouraged and adapted to individual needs.