Cyclin D3 promotes pancreatic ß-cell fitness and viability in a cell cycle-independent manner and is targeted in autoimmune diabetes.

Type 1 diabetes is an autoimmune condition caused by the lymphocyte-mediated destruction of the insulin-producing ß cells in pancreatic islets. We aimed to identify final molecular entities targeted by the autoimmune assault on pancreatic ß cells that are causally related to ß cell viability. Here, we show that cyclin D3 is targeted by the autoimmune attack on pancreatic ß cells in vivo. Cyclin D3 is down-regulated in a dose-dependent manner in ß cells by leukocyte infiltration into the islets of the nonobese diabetic (NOD) type 1 diabetes-prone mouse model. Furthermore, we established a direct in vivo causal link between cyclin D3 expression levels and ß-cell fitness and viability in the NOD mice. We found that changes in cyclin D3 expression levels in vivo altered the ß-cell apoptosis rates, ß-cell area homeostasis, and ß-cell sensitivity to glucose without affecting ß-cell proliferation in the NOD mice. Cyclin D3-deficient NOD mice exhibited exacerbated diabetes and impaired glucose responsiveness; conversely, transgenic NOD mice overexpressing cyclin D3 in ß cells exhibited mild diabetes and improved glucose responsiveness. Overexpression of cyclin D3 in ß cells of cyclin D3-deficient mice rescued them from the exacerbated diabetes observed in transgene-negative littermates. Moreover, cyclin D3 overexpression protected the NOD-derived insulinoma NIT-1 cell line from cytokine-induced apoptosis. Here, for the first time to our knowledge, cyclin D3 is identified as a key molecule targeted by autoimmunity that plays a nonredundant, protective, and cell cycle-independent role in ß cells against inflammation-induced apoptosis and confers metabolic fitness to these cells.

Systematic Review on the Correlation Between SARS-CoV-2 Real-Time PCR Cycle Threshold Values and Epidemiological Trends.

BACKGROUND: The ability to proactively predict the epidemiological dynamics of infectious diseases such as coronavirus disease 2019 (COVID-19) would facilitate efficient public health responses and may help guide patient management. Viral loads of infected people correlate with infectiousness and, therefore, could be used to predict future case rates. AIM: In this systematic review, we determine whether there is a correlation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) real-time reverse-transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) values (a proxy for viral load) and epidemiological trends in patients diagnosed with COVID-19, and whether Ct values are predictive of future cases. METHODS: A PubMed search was conducted on August 22 2022, based on a search strategy of studies reporting correlations between SARS-CoV-2 Ct values and epidemiological trends. RESULTS: Data from 16 studies were relevant for inclusion. RT-PCR Ct values were measured from national (n = 3), local (n = 7), single-unit (n = 5), or closed single-unit (n = 1) samples. All studies retrospectively examined the correlation between Ct values and epidemiological trends, and seven evaluated their prediction model prospectively. Five studies used the temporal reproduction number (Rt) as the measure of the population/epidemic growth rate. Eight studies reported a prediction time in the negative cross-correlation between Ct values and new daily cases, with seven reporting a prediction time of ~1-3 weeks, and one reporting 33 days. CONCLUSION: Ct values are negatively correlated with epidemiological trends and may be useful in predicting subsequent peaks in variant waves of COVID-19 and other circulating pathogens.

CDK11 Promotes Cytokine-Induced Apoptosis in Pancreatic Beta Cells Independently of Glucose Concentration and Is Regulated by Inflammation in the NOD Mouse Model.

Background: Pancreatic islets are exposed to strong pro-apoptotic stimuli: inflammation and hyperglycemia, during the progression of the autoimmune diabetes (T1D). We found that the Cdk11(Cyclin Dependent Kinase 11) is downregulated by inflammation in the T1D prone NOD (non-obese diabetic) mouse model. The aim of this study is to determine the role of CDK11 in the pathogenesis of T1D and to assess the hierarchical relationship between CDK11 and Cyclin D3 in beta cell viability, since Cyclin D3, a natural ligand for CDK11, promotes beta cell viability and fitness in front of glucose. Methods: We studied T1D pathogenesis in NOD mice hemideficient for CDK11 (N-HTZ), and, in N-HTZ deficient for Cyclin D3 (K11HTZ-D3KO), in comparison to their respective controls (N-WT and K11WT-D3KO). Moreover, we exposed pancreatic islets to either pro-inflammatory cytokines in the presence of increasing glucose concentrations, or Thapsigargin, an Endoplasmic Reticulum (ER)-stress inducing agent, and assessed apoptotic events. The expression of key ER-stress markers (Chop, Atf4 and Bip) was also determined. Results: N-HTZ mice were significantly protected against T1D, and NS-HTZ pancreatic islets exhibited an impaired sensitivity to cytokine-induced apoptosis, regardless of glucose concentration. However, thapsigargin-induced apoptosis was not altered. Furthermore, CDK11 hemideficiency did not attenuate the exacerbation of T1D caused by Cyclin D3 deficiency. Conclusions: This study is the first to report that CDK11 is repressed in T1D as a protection mechanism against inflammation-induced apoptosis and suggests that CDK11 lies upstream Cyclin D3 signaling. We unveil the CDK11/Cyclin D3 tandem as a new potential intervention target in T1D.

The Power of Wild Plants in Feeding Humanity: A Meta-Analytic Ethnobotanical Approach in the Catalan Linguistic Area.

Wild food plants (WFP) have always been present in our kitchen, although they have not always been given the same importance as crops. In the Catalan linguistic area (CLA), covered in this paper, WFP were of great importance as a subsistence food not only during the years of the Spanish civil war (1936-1939) and World War II (1939-1945), but also long before these periods and in the years thereafter. The CLA has been well studied at the level of traditional knowledge on plant biodiversity, and much of this information is collected in a database by the EtnoBioFiC research group. The aim of this work is to carry out a meta-analysis of the WFP dataset of he CLA (only regarding edible uses, drinks excluded) and to identify the most quoted plants, and the information associated with them. With data from 1659 informants, we recorded 10,078 use reports of 291 taxa (278 of which at specific or subspecific levels and 13 only determined at generic level) belonging to 67 families. The most reported taxa, also with highest cultural importance indexes, are Thymus vulgaris, Foeniculum vulgare subsp. piperitum, Laurus nobilis, Rubus ulmifolius and Mentha spicata. The ethnobotanicity index for food plants is 6.62% and the informant consensus factor, also for food uses, is a very high 0.97, supporting the robustness of the information. The results provided and discussed in this work concern a significant part of the edible resources in the territory considered, which is, often and mainly, underestimated and underutilised. Its consideration could be an opportunity to promote closer and more sustainable agriculture. From the state-of-the-art of this question, it is possible to propose old, in some cases forgotten foods that could be newly introduced onto the market, first, but not only, at a local level, which could be interesting for new crop development in the frame of a valorisation of territorial identity.

[Cancer cluster analysis. The case of the Campdorà District in Girona, Spain]. / Análisis de conglomerados de cancer. El caso del barrio de Campdorà, Girona.

A conglomerate of cases may be defined as the onset of a number of cases of a disease larger than would be expected for a certain population group, geographical area or a certain timeframe. In the case of cancer, the study of conglomerates entails a number of specific characteristics as compared to other groups of diseases. This work is aimed at proposing a protocol affording the possibility of conducting the study of cancer conglomerates in time and/or space. This article is illustrated with a practical application in the case of the Campdorà District in Girona. Following a proposed protocol for the study of conglomerates, a description is provided of several statistical tools making it possible to draw a comparison among the existence of time-related groupings, as well as the related risk. During the period studied (1994-2002), no excessive statistically significant number of cancer cases seemed to have occurred in the Campdorà District in Girona.

Análisis de conglomerados de cáncer. El caso del barrio de Campdorà, Girona / Cancer Cluster Analysis. the Case of the Campdorà District in Girona, Spain

Un conglomerado de casos puede definirse como la aparición deun número de casos de una enfermedad en una cantidad superior a laque se esperaría para un determinado grupo de población, un áreageográfica y un período de tiempo determinado. En el caso del cáncerel estudio de conglomerados presenta una serie de característicasespecíficas respecto a otras agrupaciones de enfermedades. El objetivode este trabajo es proponer un protocolo que permita desarrollarel estudio de conglomerados de cáncer en el tiempo y/o en el espacio.Ilustramos la nota con una aplicación práctica en el caso del barrio deCampdorà, Girona. Tras proponer un protocolo para el estudio deconglomerados, describimos varios instrumentos estadísticos quepermiten contrastar la existencia de agrupaciones temporales, asícomo el riesgo asociado. Durante el período considerado, 1994-2002, no pareció haber ocurrido de forma estadísticamente significativa,un exceso de casos de cáncer en el barrio de Campdorà de Girona

A conglomerate of cases may be defined as the onset of a numberof cases of a disease larger than would be expected for a certainpopulation group, geographical area or a certain timeframe. In thecase of cancer, the study of conglomerates entails a number of specificcharacteristics as compared to other groups of diseases. Thiswork is aimed at proposing a protocol affording the possibility ofconducting the study of cancer conglomerates in time and/or space.This article is illustrated with a practical application in the case ofthe Campdorà District in Girona. Following a proposed protocolfor the study of conglomerates, a description is provided of severalstatistical tools making it possible to draw a comparison among theexistence of time-related groupings, as well as the related risk.During the period studied (1994-2002), no excessive statisticallysignificant number of cancer cases seemed to have occurred inthe Campdorà District in Girona