Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm defined by the presence of t(9;22) translocation whose origin has been associated with the tridimensional genome organization. This ...rearrangement leads to the fusion of BCR and ABL1 genes giving rise to a chimeric protein with constitutive kinase activity. Imatinib, a tyrosine kinase inhibitor (TKI), is used as a first‐line treatment for CML, though ~40% of CML patients do not respond. Here, using structured illumination microscopy (SIM) and 3D reconstruction, we studied the 3D organization patterns of the ABL1 and BCR genes, and their chromosome territories (CTs) CT9 and CT22, in CD34+ cells from CML patients that responded or not to TKI. We found that TKI resistance in CML is associated with high levels of structural disruption of CT9 and CT22 in CD34+ cells, increased CT volumes (especially for CT22), intermingling between CT9 and CT22, and an open‐chromatin epigenetic mark in CT22. Altogether our results suggest that large‐scale disruption of CT9 and CT22 correlates with the clinical response of CML patients, which could be translated into a potential prognostic marker of response to treatment in this disease and provide novel insights into the mechanisms underlying resistance to TKI in CML.
What's new?
The t(9;22) translocation and resulting encoding of a chimeric protein with constitutive tyrosine kinase activity is a hallmark of chronic myeloid leukaemia (CML). The genesis of this rearrangement is related to the topological organization of chromatin in the nucleus. Using super‐resolution microscopy, the authors studied the topological features of bone marrow stem cells from CML patients. They found that disruption of chromosome territories 9 and 22 associates with non‐response to tyrosine kinase inhibitors in CML. The results suggest a novel prognostic marker and provide new insights into the mechanisms underlying treatment resistance in CML and regulation of the 3D genome organization.
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•Polarized excitation light effects in Raman spectra of liquids samples.•Circular and linear polarization states of the excitation light.•Intensity increases of the Raman bands when ...circular polarization is used.•Circular and linear polarization help to understand the nature of the molecular vibrations.•Circular polarization can be useful for the identification of components in mixtures at low concentrations.
The polarization state of the excitation light used in two Raman systems was controlled to study its effect in the unpolarized Raman spectra of unstructured samples. Both systems work in different regions of the electromagnetic spectrum (NIR and visible). Four polarization states (linear, linear at 45° and 90°, and circular) were used to excite liquid samples (ethanol, acetone, and their mixture). The results show that the Raman peaks intensities’ ratio varies according to the polarization state of the excitation light. Peaks related to functional groups and C-H stretching modes increase their intensity when circular polarization (CP) is applied. The latter may help to study liquid mixtures with low concentrations. Different polarizing light states give a more detailed spectroscopic analysis since it gathers more structural information of the samples tested in this work with an undefined structure.
A collimated transmission beam interferometer is used to measure the water motion provoked by the fish swimming through it. An indirect measurement of the fish motion impact in the water contained in ...a home-type aquarium is detected. Measurements of the whole aquarium are possible due to a large diameter collimated laser beam in the interferometer's object arm. This beam goes through the aquarium, and any perturbation inside it deflects the collimated beam. The interferometer detects a phase difference, i.e., the beam through the disturbed water undergoes different optical paths. This optical phase change was first demonstrated by means of a simple test using spherical steel marbles placed in a cuvette. For this, the small water movements for a single steel marble are detected with the acquired optical phase. Next, the aquarium optical phase results show water movements according to the fishes' size and swimming speed. It is worth mentioning that no additives were added to the aquarium's fresh water during the tests, so the water was crystal clear.
The variability in Helicobacter pylori vacA and cagA genes has been related to the progression of the gastrointestinal disease; also the presence of H. pylori in the oral cavity has been associated ...with periodontal disease in adults, but, in children without dyspeptic symptoms, little is known about this. We evaluated the prevalence of H. pylori and the presence of vacA/cagA genotypes in the oral cavity of Mexican children without dyspeptic symptoms. The gingival status was measured, and dental plaque samples (n=100) were taken. 38% of children were positive for H. pylori 16S rRNA gene by qPCR. A significant association between H. pylori oral infection and gingival status was observed (P<0.001). In 34.6% (9/26) of mild gingivitis cases, s1m2 genotype was found, while s1m1 was typed in 50% (3/6) of moderate gingivitis. The cagA prevalence among H. pylori-positive children was 80.8% (21/26), 83.3% (5/6), and 16.7% (1/6) of cases of mild gingivitis, moderate gingivitis, and nongingivitis, respectively (P<0.001). The s1m1/cagA+ combinational genotype was the most detected in children with gingivitis. Our results suggest that the prevalence of H. pylori and detection of vacA/cagA genotypes-associated gastrointestinal disease in the oral cavity could be related to the progression of gingivitis in asymptomatic children.
A bone's fracture could be produced by an excessive, repetitive, or sudden load. A regular medical practice to heal it is to fix it in two possible ways: external immobilization, using a ferule, or ...an internal fixation, using a prosthetic device commonly attached to the bone by means of surgical screws. The bone's volume loss due to this drilling modifies its structure either in the presence or absence of a fracture. To observe the bone's surface behavior caused by the drilling effects, a digital holographic interferometer is used to analyze the displacement surface's variations in nonfractured post-mortem porcine femoral bones. Several nondrilled post-mortem bones are compressed and compared to a set of post-mortem bones with a different number of cortical drillings. During each compression test, a series of digital interferometric holograms were recorded using a high-speed CMOS camera. The results are presented as pseudo 3D mesh displacement maps for comparisons in the physiological range of load (30 and 50 lbs) and beyond (100, 200, and 400 lbs). The high resolution of the optical phase gives a better understanding about the bone's microstructural modifications. Finally, a relationship between compression load and bone volume loss due to the drilling was observed. The results prove that digital holographic interferometry is a viable technique to study the conditions that avoid the surgical screw from loosening in medical procedures of this kind.
Serotonin 2C receptors (5HT2C) are involved in serotonin-driven dynamic equilibrium adjustments responsible for homeostatic stability in brain structures that modulate behavior and emotions. Single ...nucleotide polymorphisms (SNPs) from the serotonin 2C receptor gene (HTR2C) have been associated with several neurological and mental disorders, including abnormalities in cognitive and emotional processes. The aim of this study was to evaluate the association between the rs6318 SNP of the HTR2C gene and behavioral characteristics exhibited by children and adolescents based on the Child Behavior Checklist (CBCL/6-18) inventory. Eighty-five psychiatric outpatients between 8 and 18 years of age underwent genotyping of the rs6318 SNP. The CBCL/6-18 scale was administered to their caregivers. The chi-squared test was used to assess differences in the frequency of C and G alleles of the rs6318 SNP relative to the grouped CBCL/6-18 scores; significance level was 5%. The presence of the G allele of rs6318 was found to be associated with characteristics of aggressive behavior and social problems, and aggressive behavior was found to be associated with heterozygosis in females. These findings contribute to the identification of mental and behavioral phenotypes associated with gene expression.
To determine potential predictors of long‐term survival in a large set of Hispanic (Mexican) patients with chronic myeloid leukemia (CML) treated with imatinib. We conducted an analysis with data ...from 411 patients with CML treated at the National Cancer Institute – Mexico, between January 2000 and December 2016. We found a median age at diagnosis of 40 years (range: 18‐84 years). The survival rate at 150 months was 82.02%, and we found that phase at diagnosis (β: 0.447, 95% Confidence Interval 95% CI: 0.088, 0.806; P = 0.015), prognostic scales (Sokal P = 0.021 and Hasford β: 0.369, 95% CI: 0.049, 0.688; P = 0.024) and hematological response at 3 months (β: 0.717, 95% CI: 0.443, 0.991; P < 0.001), but not molecular response (P = 0.834 for 6 months, P = 0.927 for 12 months, P = 0.250 for 18 months), were independently associated with overall survival. Survival analysis in subsets, according to the initial phase (chronic, accelerated and blastic phase) did not show any effect according to prognostic scales (P > 0.05). Mexican patients with CML have repeatedly been diagnosed at earlier ages. Prognostic factors in CML may differ according to the ethnic or geographical context. We found that phase at diagnosis, prognostic scale and hematological response at 3 months were independent predictors of survival.
We conducted an overall survival analysis with data from 411 patients with CML treated at the National Cancer Institute – Mexico, between January 2000 and December 2016. Phase at diagnosis, prognostic scale and hematological response at 3 months were independent predictors of survival in Mexican patients with CML treated with Imatinib.
Bee honey is an exceptionally nutritious food with unique chemical and mineral contents. This report introduces the use of the second-harmonic generation (SHG) microscopy for imaging honey sugar ...crystals' morphology as an alternative for its authentication process. The crystals and their boundaries are clearly observed with SHG compared with bright-field microscopy, where the liquid honey avoids the visualization of a sharp image. Four different honey samples of Mexico's various floral origins and geographical regions are analyzed in our study. These samples are representative of the diversity and valuable quality of bee honey production. The SHG image information is complemented with Raman spectroscopy (RS) analysis, since this optical technique is widely used to validate the bee's honey composition stated by its floral origin. We relate the SHG imaging of honey crystals with the well-defined fructose and glucose peaks measured by RS. Size measurement is introduced using the crystal´s length ratio to differentiate its floral origin. From our observations, we can state that SHG is a promising and suitable technique to provide a sort of optical fingerprint based on the floral origin of bee honey.
Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens that cause mild or serious diseases and can lead to people death. This study reports the prevalence and characteristics of STEC ...O157 and non-O157 in commercial ground beef and environmental samples, including meat table, knife, meat mincing machine, and manipulator hands (n = 450) obtained from 90 retail markets over a nine-month period. The STEC isolates were serotyped and virulence genes as stx (Shiga toxin), rfb(O157) (O157 lipopolysaccharide), fliC(H7) (H7 flagellin), eae (intimin), ehxA (enterohemolysin) and saa (STEC autoagglutinating adhesin), were determined. STEC O157 were identified in 23 (25.5%) beef samples and 16 (4.4%) environmental samples, while STEC non-O157 were present in 47 (52.2%) and 182 (50.5%), respectively. Among 54 strains isolated, 17 were STEC O157:H7 and 37 were STEC non-O157. The prevalent genotype for O157 was stx(2)/eae/ehxA/fliC(H7) (83.4%), and for STEC non-O157 the most frequent ones were stx(1)/stx(2)/saa/ehxA (29.7%); stx(2) (29.7%); and stx(2)/saa/ehxA (27%). None of the STEC non-O157 strains were eae-positive. Besides O157:H7, other 20 different serotypes were identified, being O8:H19, O178:H19, and O174:H28 the prevalent. Strains belonging to the same serotype could be isolated from different sources of the same retail market. Also, the same serotype could be detected in different stores. In conclusion, screening techniques are increasingly sensitive, but the isolation of STEC non-O157 is still a challenge. Moreover, with the results obtained from the present work, although more studies are needed, cross-contamination between meat and the environment could be suspected.
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