Orthodenticle Is Required for the Expression of Principal Recognition Molecules That Control Axon Targeting in the Drosophila Retina

Parallel processing of neuronal inputs relies on assembling neural circuits into distinct synaptic-columns and layers. This is orchestrated by matching recognition molecules between afferent growth cones and target areas. Controlling the expression of these molecules during development is crucial but not well understood. The developing Drosophila visual system is a powerful genetic model for addressing this question. In this model system, the achromatic R1-6 photoreceptors project their axons in the lamina while the R7 and R8 photoreceptors, which are involved in colour detection, project their axons to two distinct synaptic-layers in the medulla. Here we show that the conserved homeodomain transcription factor Orthodenticle (Otd), which in the eye is a main regulator of rhodopsin expression, is also required for R1-6 photoreceptor synaptic-column specific innervation of the lamina. Our data indicate that otd function in these photoreceptors is largely mediated by the recognition molecules flamingo (fmi) and golden goal (gogo). In addition, we find that otd regulates synaptic-layer targeting of R8. We demonstrate that during this process, otd and the R8-specific transcription factor senseless/Gfi1 (sens) function as independent transcriptional inputs that are required for the expression of fmi, gogo and the adhesion molecule capricious (caps), which govern R8 synaptic-layer targeting. Our work therefore demonstrates that otd is a main component of the gene regulatory network that regulates synaptic-column and layer targeting in the fly visual system

Postharvest Ozone Fumigation of Grapes (cv Sangiovese) Differently Affects Volatile Organic Compounds and Polyphenol Profiles of Berries and Wine

Consumers are more and more oriented towards the purchase of safer food and beverages, which is pushing the wine sector to find alternatives to the use of sulfur dioxide. Ozone (O3) is already applied in the wine industry to produce sulfur dioxide-free wines through the patented method Purovino®. The aim of this two-year study was that of evaluating whether the postharvest treatment of grapes with ozone affects volatile organic compounds (VOCs) and polyphenol profile in berries, and in turn, wine composition. Grape bunches (Vitis vinifera L.) of cv Sangiovese were fumigated overnight with gaseous ozone (max 20 g·h−1 with 6% w.w−1 of ozone) in a cold room at 4°C (±0.5). After treatment, grapes were processed into wine. In grapes, ozone treatments increased total polyphenol and flavonoid content and upregulated specific genes (phenylalanine ammonia lyase, VvPAL, flavanol synthase 1, and VvFLS1) involved in polyphenol biosynthesis. Wine obtained from ozone-treated grapes had higher flavanol content than the control. Fumigation only slightly affected the different VOC classes of grapes and wine, including aroma compounds derived from the lipoxygenase (LOX) pathway. Although a season-dependent effect was observed, results showed that postharvest ozone treatments applied to avoid the use of sulfur dioxide introduced limited but, in general, positive modifications to grape and wine composition. This information provides assurance to winemakers that the maintenance of wine quality and typicity will be guaranteed when using ozone treatments

Multidisciplinarity in Transition Pathways for Patients With Kidney Disease: The Current State of Play

In the field of medical care, successful transition from pediatric-centered to adult-oriented healthcare can provide a sense of continuity in the development of youth, and prepare them to accept responsibility for and manage their own chronic kidney condition in complete autonomy. The so-called transition process requires the presence of some basic aspects: a multidisciplinary team, which acts as a bridge between child and adult services; a comprehensive clinical, cognitive, psychological, and social change for the young people; the involvement of family and caregivers. Within the framework of transition and chronicity during the developmental age, we selected international papers explaining models which agreed on some important steps in the transition process, although many differences can be observed between different countries. In fact, in Europe, the situation appears to be heterogeneous as regards certain aspects: the written transition plan, the educational programmes, the timing of transfer to adult services, the presence of a transition coordinator, a dedicated off-site transition clinic. We then analyzed some studies focusing on patients with renal diseases, including the first to contain a standardized protocol for transition which was launched recently in the USA, and which seems to have already achieved important positive, although limited, results. In Italy, the issue of transition is still in its infancy, however important efforts in the management of chronic kidney disease have already been initiated in some regions, including Emila Romagna, which gives us hope for the future of many young people

Enhancement of lysosomal glycohydrolase activity in human primary B lymphocytes during spontaneous apoptosis.

It has been shown that lysosomes are involved in B cell apoptosis but lysosomal glycohydrolases have never been investigated during this event. In this study we determined the enzymatic activities of some lysosomal glycohydrolases in human tonsil B lymphocytes (TBL) undergoing in vitro spontaneous apoptosis. Fluorimetric methods were used to evaluate the activities of β-hexosaminidases, α-mannosidase, β-mannosidase, β-galactosidase, β-glucuronidase and α-fucosidase. Results show that in TBL during spontaneous apoptosis, there is a significant increase in the activity of β-hexosaminidases, α-mannosidase, β-mannosidase and β-galactosidase. Also β-glucuronidase and α-fucosidase activities increase but not in a significant manner. Further studies on β-hexosaminidases revealed that also mRNA expression of the α- and β-subunits, which constitute these enzymes, increases during spontaneous TBL apoptosis. When TBL are protected from apoptosis by the thiol molecule N-acetyl-L-cysteine (NAC), there is no longer any increase in glycohydrolase activities and mRNA expression of β-hexosaminidase α- and β-subunits. This study demonstrates for the first time that the activities and expression of some lysosomal glycohydrolases are enhanced in TBL during spontaneous apoptosis and that these increases are prevented when TBL apoptosis is inhibited

Born with a solitary kidney : at risk of hypertension

Background: Subjects with a congenital solitary kidney (CSK) are believed to be at risk of hypertension due to their low number of nephrons. However, as CSK is a congenital abnormality of the kidney or urinary tract (CAKUT), subtle dysplastic changes contributing to hypertension cannot be excluded. Methods: We retrospectively compared office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) between two groups of children with CAKUT, aged 6\u201318 years: Group A with a CSK and Group B with two kidneys. All had normal renal parenchyma on scintigraphy and normal renal function. OBP and mean systolic and diastolic 24-h, daytime and nighttime ambulatory BP records were analyzed. The distribution of OBP and APBM as continuous values and the prevalence of hypertension (ambulatory/severe ambulatory or masked hypertension) in the two groups were compared. Results: There were 81 patients in Group A and 45 in Group B. Median OBP standard deviation scores were normal in both groups, without significant differences. Median ABPM standard deviation scores, although normal, were significantly higher in Group A and the prevalence of hypertension was higher (ambulatory/severe ambulatory or masked) (33.3 vs. 13.3%, p = 0.019), mainly because of the greater occurrence of masked hypertension. Conclusions: Our data show that a CSK per se can be associated with an increased risk of hypertension from the pediatric age. Therefore, ABPM, which has proved valuable in the screening of hypertension, is warranted in children with a CSK, even if laboratory and imaging assessment is otherwise normal

Identifying Wine Grape Aromatic Maturity using E-nose and GC-MS: the case of Nerello Mascalese Grapes from two Contrade of the Etna Area

A study of aromatic maturity of Nerello Mascalese grapes from two districts ("Contrade") of the Etna area was carried out using gas chromatography-mass spectrometry (GC-MS) and electronic nose (E-nose). To validate our hypothesis regarding the potential use of E-nose for aromatic maturity, two vineyards with different characteristics (08 Alto and Solicchiata) were used. Grapes were sampled at 18°, 21° and 23°Brix. Regarding the phenol maturity index, total anthocyanins reached a peak at the second sampling in 08 Alto grapes, while in Solicchiata they constantly increased. The ratio total anthocyanins: total polyphenols in 08 Alto grapes increased from 0.14 to 0.33, and in Solicchiata from 0.17 to 0.23. As regards grape volatile organic compounds (GVOCs) for the aromatic maturity index, in Solicchiata the concentrations of glycosylated benzenoids and C13-norisoprenoids were much higher than in 08 Alto, and the concentration decreased during maturity (opposite trend to the anthocyanins); by contrast, in 08 Alto, concentrations peaked at the second sampling time (as with the anthocyanins). The E-nose results did not completely coincide with the GVOCs pattern, but they discriminated the maturity stages very well. However, the different metallo-porphyrins responded differently depending on the class of GVOCs, highlighting very promising results in terms of GVOCs non-destructive prediction by means of principal component regression (PCR) application. E-nose shows potential for easy use with rapid PCR for the monitoring of the aromatic maturity of Nerello Mascalese grapes

History and phylogeny of intermediate filaments: Now in insects

Intermediate filaments include the nuclear lamins, which are universal in metazoans, and the cytoplasmic intermediate filaments, which are much more varied and form cell type-specific networks in animal cells. Until now, it has been thought that insects harbor lamins only. This view is fundamentally challenged by the discovery, reported in BMC Biology, of an intermediate filament-like cytoplasmic protein, isomin, in the hexapod Isotomurus maculatus. Here we briefly review the history of research on intermediate filaments, and discuss the implications of this latest finding in the context of what is known of their structure and functions

Expanding phenotype of schimke immuno-osseous dysplasia: Congenital anomalies of the kidneys and of the urinary tract and alteration of nk cells

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype\u2013genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD\u2014both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7R\u3b1 expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies

RanBP1 Couples Nuclear Export and Golgi Regulation through LKB1 to Promote Cortical Neuron Polarity

Neuronal polarity in the developing cortex begins during the early stages of neural progenitor migration toward the cortical plate and culminates with the specification of the axon and dendrites. Here, we demonstrate that the Ran-dependent nucleocytoplasmic transport machinery is essential for the establishment of cortical neuron polarity. We found that Ran-binding protein 1 (RanBP1) regulates axon specification and dendritic arborization in cultured neurons in vitro and radial neural migration in vivo. During axonogenesis, RanBP1 regulates the cytoplasmic levels of the polarity protein LKB1/Par4, and this is dependent on the nuclear export machinery. Our results show that downstream of RanBP1, LKB1 function is mediated by the STK25-GM130 pathway, which promotes axonogenesis through Golgi regulation. Our results indicate that the nucleocytoplasmic transport machinery is a main regulator of neuron polarity, including radial migration, and that the regulated export of LKB1 through RanBP1 is a limiting step of axonogenesis

Regional Precuneus Cortical Hyperexcitability in Alzheimer's Disease Patients

Objective: Neuronal excitation/inhibition (E/I) imbalance is a potential cause of neuronal network malfunctioning in Alzheimer's disease (AD), contributing to cognitive dysfunction. Here, we used a novel approach combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to probe cortical excitability in different brain areas known to be directly involved in AD pathology. Methods: We performed TMS-EEG recordings targeting the left dorsolateral prefrontal cortex (l-DLPFC), the left posterior parietal cortex (l-PPC), and the precuneus (PC) in a large sample of patients with mild-to-moderate AD (n = 65) that were compared with a group of age-matched healthy controls (n = 21). Results: We found that patients with AD are characterized by a regional cortical hyperexcitability in the PC and, to some extent, in the frontal lobe, as measured by TMS-evoked potentials. Notably, cortical excitability assessed over the l-PPC was comparable between the 2 groups. Furthermore, we found that the individual level of PC excitability was associated with the level of cognitive impairment, as measured with Mini-Mental State Examination, and with corticospinal fluid levels of Aβ42 . Interpretation: Our data provide novel evidence that precuneus cortical hyperexcitability is a key feature of synaptic dysfunction in patients with AD. The current results point to the combined approach of TMS and EEG as a novel promising technique to measure hyperexcitability in patients with AD. This index could represent a useful biomarker to stage disease severity and evaluate response to novel therapies. ANN NEUROL 2022