Revista de diagnóstico y biomarcadores moleculares

Small variations in magnetic fields can be environmental stresses. For example cell phones, which give off very weak magnetic fields. It is a question, whether these magnetic fields cause brain tumors in cell-phone users. We can model cancer as invasion from social, through psychological to deepest molecular level by Ricci flow. Mechanism of integrated stress response starts with rapid hormone induced changes in receptor conformation which lead to slower modulations of gene transcription. Inhibition of programmed cell death is a major aspect of tumorigenesis (by oncogenic transcription factors NF-kB, STAT3) through upregulation of survival genes. The afferent input from the limbic network conveys purely psychological stress reactions to the HPA axis. Even dominant oncogenes such as v- Src or K-Ras are unable to induce cancer in adult animals without injury. A strong tumor-associated inflammatory response is initiated by the dynamics of Ricci flow collapsing into an injury point that becomes a rounder cellular dysfunction. Tufts biologists show bioelectrical signals control tumors arising from cancer-causing genes; fatty acid involved in process. The have proved, that cancer, bioelectrical signals and the microbiome are connected.

Y-STR genotyping is an excellent tool for the identification of male DNA masked by female DNA, particularly in sexual assault cases where, more often the male and female components cannot be separated completely. Resultant, the female component could exist prominently even in the male component after separation. When the "male DNA sample mixed with female DNA” undergoes PCR by using autosomal STR multiplex amplification process, the female DNA component is also amplified, mostly masking the male DNA. Recently launched Y-STR kit, PowerPlex Y23 (PP Y23) System is a 5-dye multiplex genotyping kit that analyzes 17 Y-STR loci, commonly available in other Y-STR multiplex kits (DYS19, DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, and Y-GATA-H4) along with that 6 new Y-STR loci (DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643). The addition of 6 new markers has made the Y-STR analysis more discriminating. The purpose of the present study is to show the amplification of male DNA from a wide variety of forensic samples using half the manufacturer’s recommended reaction volume. Also the present study validates the kit for its use in Forensic casework. The results demonstrate that the PPY23 System is a robust and sensitive multiplex system, capable of giving reliable and consistent amplification results from a wide variety of forensic casework samples. Even the presence of high concentration of commonly encountered inhibitors such as hematin (from Blood) and humic acid (from soil), male/female DNA mixtures and low amounts of DNA template (15.62 pg) could not hamper the process of amplification.

Background: Cell-free DNA (cfDNA) analysis in maternal blood for the detection of fetal Down syndrome is gradually replacing first trimester screening. We present here a large clinical series of 10,000 consecutive pregnancies.

Objectives: To study the reliability of cell-free DNA (cfDNA) analysis in maternal blood for the detection of fetal trisomy 21, 18 and 13 in a clinical setting in 10,000 consecutive pregnancies with variable risk. cfDNA testing has been evaluated in an increasing number of pregnancies mainly at high risk for fetal trisomy, and some studies have suggested that its positive predictive value (PPV) might be lower in low-risk populations.

Study design: CfDNA testing using the Harmony™ Prenatal Test was performed in 10,000 consecutive pregnancies with high or low a-priori risk for fetal trisomy 21, 18 and 13.

Results: In 147 (1.47%) of the 10,000 pregnancies a high-risk cfDNA testing result indicated trisomy 21 (n=121), trisomy 18 (n=15) or trisomy 13 (n=11). It failed to detect 5 trisomies (2 trisomies 21, 2 trisomies 18, and 1 trisomy 13). Five false-positive results were recorded (4 in the high and 1 in the low risk population). The overall positive predictive value (PPV) was 96%, with a PPV of 96% in the high-risk (>1/200) population and 97% in the low risk (<1/200) population.

Conclusions: In this large clinical series of 10,000 consecutive pregnancies, cfDNA testing proved very reliable in detecting fetal trisomy 21, 18 and 13, with a very high PPV both in high and low risk populations.

Cerebellopontine angle medulloblastoma is a very uncommon presentation of medulloblastoma, especially in children. We report such a case in a 14-year-old boy. Clinical onset by acute hearing loss and MRI features were, furthermore, unusual findings. The tumour had an homogeneous signal on T1 and FLAIR sequences a high-signal intensity on diffusion-weighted images with slightly restricted ADC value (0.85 × 10³ mm²/s) and enhanced slightly and homogeneously after contrast. A subtotal removal of the tumour, followed by entire neuroaxis irradiation and chemotherapy were achieved. MRI data of the literature reported cases were reviewed. Features on conventional MRI sequences do not allow differentiating CPA medulloblastoma from other rare tumour of this location. We point out that ADC value and Spectroscopy might be useful differentiating CPA tumours, especially from ependymoma in children.

The animal gut has co-evolved with the microbes and parasites leading to an increased tolerance to their existence therein. Their peaceful co-existence has been a subject of research in the recent years to decipher their probabilities in multidimensional applications ranging from eradicating the helminths without affecting gut homeostasis or using helminths as therapeutics. Negligence in any one of the components of the animal gut can lead to unhealthy gut ecosystems often manifesting a diseased state. Supply of key nutrients, synthesis of vitamins, resistance to invasion by pathogens and helping in hatching of helminth eggs are some important services provided by the gut bacteria that may well be utilised by the helminth. The gut bacteria thus seem to be exploited by the helminths for establishment of infection in the host. However, relationships are not as simple as it seems. The paper tries to present different aspects of this host-bacteria-helminth relationship and their future perspectives.

Diabetes mellitus is a widespread disease which an estimated 285 million people in the world suffer from, and these numbers are on the rise making it one of the largest threats to human health in the coming decades. Early research has shown that restoration of the β cell mass by either stimulating β cell replication or β cell neogenesis may be a viable strategy in diabetes therapy. Some proteins such as the INGAP (hamster Reg3delta) have been shown to be involved in β cell regeneration and therefore may be potential sources of new drugs for diabetes treatment. The INGAP protein and peptide as well as other members of the Reg3 family of proteins such as HIP (human Reg3alpha/β) have been shown to have an effect on β cell regeneration, however this effect as well as their mechanism of action in the pancreas is unclear. This review described current knowledge about the mechanism of action and activity of INGAP and other members of the Reg3 family of proteins in β cell regeneration.

The CRISPR/Cas9 (Clustered Regions of Interspersed Palindromic Repeats-Cas9, consists of a DNA-nuclease and a piece of RNA that homes in on a DNA sequence, enabling investigators to create precisely targeted mutations, corrections to mutations, or other gene modulation. CRISPR/Cas9 is an ancient anti-viral immune system found in bacteria and archaea. The immediate assumption would be that it is a primitive innate immune system like a restriction enzyme defense system known since 1970 and is the backbone of the gene cloning methods Surprisingly, it is a sophisticated adaptive immune system very different from the somatic gene recombination, which is wellknown and is found in higher vertebrate animals as T and B lymphocytes. This amazing newly discovered CRISPR has emerged as a magnum opus of programmable nuclease technology for the precise editing of the genome in cells. This new genome editing tool is much more robust to customize and optimize because the site selection for DNA cleavage is guided by a short sequence of RNA. Even though this tool still has some imperfections and suffers from some off-target effects, the CRISPR/Cas9 system has been widely and successfully applied as a biotechnology in a number of areas. This technology is being considered to edit defective genes in human embryos and to create specific DNA fragment insertions for correcting numerous genetic diseases. The following section is a brief history and development of the CRISPR system and shows its potential future applications. We believe that the readers will benefit greatly from the information of this newly discovered prokaryotic adaptive immunity system, and we believe that in the very near future this technology will be widely used in clinics and research.

Farnesoid X receptor (FXR), the bile acid-activated nuclear receptor and member of the nuclear receptor superfamily, plays a key role in bile acid, lipid and glucose homeostasis. FXR is abundantly expressed in the kidney, but its physiological function remains mostly unknown. Recent studies have demonstrated that FXR is expressed in renal collecting ducts where it directly regulates the transcription of the aquaporin 2 (AQP2) gene. FXR gene deficiency results in a polyuric phenotype in mice. These results highlight a novel mechanism for FXR in mediating renal urine concentration independent of the antidiuretic hormone (ADH) system. FXR may represent a potential therapeutic target for treating diseases with urine concentrating defect, including hepatorenal syndrome and nephrogenic diabetes insipitus.