BRAF and TERT mutations in papillary thyroid cancer patients of Latino ancestry.

Papillary thyroid cancer (PTC) is the second most commonly diagnosed malignancy in U.S. Latinas and in Colombian women. Studies in non-Latinos indicate that BRAF and TERT mutations are PTC prognostic markers. This study aimed to determine the prevalence and clinical associations of BRAF and TERT mutations in PTC Latino patients from Colombia. We analyzed mutations of BRAF (V600E) and TERT promoter (C228T, C250T) in tumor DNA from 141 patients (75 with classical variant PTC, CVPTC; 66 with follicular variant PTC, FVPTC) recruited through a multi-center study. Associations between mutations and clinical variables were evaluated with Fisher exact tests. Survival was evaluated with Kaplan-Meier plots. Double-mutant tumors (BRAF+/TERT+, n = 14 patients) were more common in CVPTC (P = 0.02). Relative to patients without mutations (n = 48), double mutations were more common in patients with large tumors (P = 0.03), lymph node metastasis (P = 0.01), extra-thyroid extension (P = 0.03), and advanced stage (P = 6.0 × 10-5). In older patients, TERT mutations were more frequent (mean age 51 years vs 45 years for wild type TERT, P = 0.04) and survival was lower (HR = 1.20; P = 0.017); however, given the small sample size, the decrease in survival was not statically significant between genotypes. Comparisons with published data in US whites revealed that Colombian patients had a higher prevalence of severe pathological features and of double-mutant tumors (10 vs 6%, P = 0.001). Mutations in both oncogenes show prognostic associations in Latinos from Colombia. Our study is important to advance Latino PTC precision medicine and replicates previous prognostic associations between BRAF and TERT in this population

The HABP2 G534E polymorphism does not increase nonmedullary thyroid cancer risk in Hispanics.

Familial nonmedullary thyroid cancer (NMTC) has not been clearly linked to causal germline variants, despite the large role that genetic factors play in risk. Recently, HABP2 G534E (rs7080536A) has been implicated as a causal variant in NMTC. We have previously shown that the HABP2 G534E variant is not associated with TC risk in patients from the British Isles. Hispanics are the largest and the youngest minority in the United States and NMTC is now the second most common malignancy in women from this population. In order to determine if the HABP2 G534E variant played a role in NMTC risk among Hispanic populations, we analyzed 281 cases and 1105 population-matched controls from a multicenter study in Colombia, evaluating the association through logistic regression. We found that the HABP2 G534E variant was not significantly associated with NMTC risk (P=0.843) in this Hispanic group. We also stratified available clinical data by multiple available clinicopathological variables and further analyzed the effect of HABP2 on NMTC presentation. However, we failed to detect associations between HABP2 G534E and NMTC risk, regardless of disease presentation (P≥0.273 for all cases). Therefore, without any significant associations between the HABP2 G534E variant and NMTC risk, we conclude that the variant is not causal of NMTC in this Hispanic population

Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion

PMCID: PMC3544714This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Non-cell-autonomous regulation of interneuron specification mediated by extracellular vesicles

Disruption in neurogenesis and neuronal migration can influence the assembly of cortical circuits, affecting the excitatory-inhibitory balance and resulting in neurodevelopmental and neuropsychiatric disorders. Using ventral cerebral organoids and dorsoventral cerebral assembloids with mutations in the extracellular matrix gene LGALS3BP, we show that extracellular vesicles released into the extracellular environment regulate the molecular differentiation of neurons, resulting in alterations in migratory dynamics. To investigate how extracellular vesicles affect neuronal specification and migration dynamics, we collected extracellular vesicles from ventral cerebral organoids carrying a mutation in LGALS3BP, previously identified in individuals with cortical malformations and neuropsychiatric disorders. These results revealed differences in protein composition and changes in dorsoventral patterning. Proteins associated with cell fate decision, neuronal migration, and extracellular matrix composition were altered in mutant extracellular vesicles. Moreover, we show that treatment with extracellular vesicles changes the transcriptomic profile in neural progenitor cells. Our results indicate that neuronal molecular differentiation can be influenced by extracellular vesicles

Differentiation and multipotential characteristics of mesenchymal stem cells derived from adipose tissue of an endangered wild cat (Leopardus guigna)

Adipose tissue derived mesenchymal stem cells (AMSCs) had been isolated and used for cell therapy in domestic cats. For wild cats, the isolation of AMSCs has only been reported in the black-footed cat (Felis nigripes). AMSCs obtained from wild cats may be useful to treat injuries of endangered cat species that remain in captivity or arrive at wildlife rehabilitation centers. Additionally, AMSCs might allow improvement of cloning techniques or assist in derivation of induced pluripotent stem cells. Endangered wild cats such as the guigna (Leopardus guigna), an endemic and endangered species from Chile and Argentina, might benefit greatly from the development of novel treatments or techniques that can be applied for its conservation. The objective of this study was to characterise putative AMSCs from guigna in terms of their main biological attributes, particularly, growth kinetics, differentiation ability and surface marker expression. Results obtained from this characterisation were compared with AMSCs isolated from domestic cats. AMSCs were isolated from peritoneal adipose tissue of female cats and subcutaneous tissue from a female guigna. Migration potential, colony-forming unit assay, mesodermal differentiation and surface marker expression (CD45, CD44, CD90, MHCI and MHCII) were evaluated. Domestic cat and guigna AMSCs displayed similar growth properties in culture. Both AMSC types showed mesodermal differentiation potential, in vitro homing potential and similar surface marker expression. These results indicate that AMSCs from subcutaneous tissue of guigna could have potential use as regenerative treatment for this species and might be considered for use in other biotechnological applications

Análisis de la densidad espectral de potencia en registros mer

Se presenta en este trabajo una metodología para el análisis armónico de señales de micro electrodos de registro MER en pacientes con enfermedad de Parkinson para el reconocimiento de zonas cerebrales. Se emplea el periodograma vía método de Welch para hallar las componentes frecuenciales propias de cada zona cerebral a fin de caracterizarlas y permitir su detección. Se utilizanclasificadores lineales para validar las características extraída

Análisis de la densidad espectral de potencia en registros mer

Se presenta en este trabajo una metodología para el análisis armónico de señales de micro electrodos de registro MER en pacientes con enfermedad de Parkinson para el reconocimiento de zonas cerebrales. Se emplea el periodograma vía método de Welch para hallar las componentes frecuenciales propias de cada zona cerebral a fin de caracterizarlas y permitir su detección. Se utilizanclasificadores lineales para validar las características extraída

Transforming growth factor-β1 impairs neuropathic pain through pleiotropic effects

<p>Abstract</p> <p>Background</p> <p>Understanding the underlying mechanisms of neuropathic pain caused by damage to the peripheral nervous system remains challenging and could lead to significantly improved therapies. Disturbance of homeostasis not only occurs at the site of injury but also extends to the spinal cord and brain involving various types of cells. Emerging data implicate neuroimmune interaction in the initiation and maintenance of chronic pain hypersensitivity.</p> <p>Results</p> <p>In this study, we sought to investigate the effects of TGF-β1, a potent anti-inflammatory cytokine, in alleviating nerve injury-induced neuropathic pain in rats. By using a well established neuropathic pain animal model (partial ligation of the sciatic nerve), we demonstrated that intrathecal infusion of recombinant TGF-β1 significantly attenuated nerve injury-induced neuropathic pain. TGF-β1 treatment not only prevents development of neuropathic pain following nerve injury, but also reverses previously established neuropathic pain conditions. The biological outcomes of TGF-β1 in this context are attributed to its pleiotropic effects. It inhibits peripheral nerve injury-induced spinal microgliosis, spinal microglial and astrocytic activation, and exhibits a powerful neuroprotective effect by preventing the induction of ATF3⁺neurons following nerve ligation, consequently reducing the expression of chemokine MCP-1 in damaged neurons. TGF-β1 treatment also suppresses nerve injury-induced inflammatory response in the spinal cord, as revealed by a reduction in cytokine expression.</p> <p>Conclusion</p> <p>Our findings revealed that TGF-β1 is effective in the treatment of neuropathic by targeting both neurons and glial cells. We suggest that therapeutic agents such as TGF-β1 having multipotent effects on different types of cells could work in synergy to regain homeostasis in local spinal cord microenvironments, therefore contributing to attenuate neuropathic pain.</p

Organización de espigas usando agrupamiento fuzzy c-means

En la caracterización de zonas cerebrales es necesario el desarrollo de procedimientos que permitan separar los potenciales de acción o espigas cuando más de una neurona es grabada con un micro electrodo de registro. El método a utilizar permite la detección, además el agrupamiento fuzzy estimará el número exacto de grupos o neuronas adyacentes al micro electrodo de registro, también determinará las plantillas de las formas de espigas presentes de forma confiable