Effects Of Alterations Research Articles

Biology of the proximal tubule in body homeostasis and kidney disease.

The proximal tubule (PT) is known as the workhorse of the kidney, both for the range and magnitude of the functions that it performs. It is not only responsible for reabsorbing most solutes and proteins filtered by glomeruli, but also for secreting non-filtered substances including drugs and uremic toxins. The PT therefore plays a pivotal role in kidney physiology and body homeostasis. Moreover, it is the major site of damage in acute kidney injury and nephrotoxicity. In this review, we will provide an introduction to the cell biology of the PT and explore how it is adapted to the execution of a myriad of different functions and how these can differ between males and females. We will then discuss how the PT regulates phosphate, glucose and acid-base balance, and the consequences of alterations in PT function for bone and cardiovascular health. Finally, we explore why the PT is vulnerable to ischemic and toxic insults, and how acute injury in the PT can lead to maladaptive repair, chronic damage, and kidney fibrosis. In summary, we will demonstrate that knowledge of the basic cell biology of the PT is critical for understanding kidney disease phenotypes and their associated systemic complications, and for developing new therapeutic strategies to prevent these.

Fish biodiversity in modified ecosystems: a case study of Nigeria's Challawa and Tiga dams in the Challawa and Kano rivers

River impoundment is usually accompanied with consequences of alteration in the hydrological system and change in the biodiversity composition of the ecosystem. This study investigated the impact of the dams built on Challawa (that is, Challawa George-Dam) and Kano (that is, Tiga Dam) on the fish biodiversity of the reservoir and below-dam sections of the two rivers. Fish sampling was done using long lines, Malian traps, cast and gill nets from stations on the reservoir and below-dam sections of the rivers. Ten fish species were identified from the reservoir and the below-dam sections of Challawa River belonging to nine families and four orders. Fish communities of the reservoir and below-dam sections of Kano River consisted of 28 species belonging to 12 families and 7 orders. Results of the Shannon diversity index (H^') indicated that the two reservoirs have relatively higher fish species diversity measures (that is, Challawa=1.948 & Kano=2.294) than the below-dam parts (that is, Challawa=1.833 & Kano=2.247) of their respective rivers. Non-metric Multidimensional Scaling (NMDS) analysis produced two-dimensional maps with stress values of 0.0554 and 0.0537, an indication that the model provided good representation of the original data in reduced-dimensional space. The ordination map indicated wide dissimilarities between fish communities of the impounded and below-dam sections. Furthermore, a one-way analysis of similarity indicated significant difference (P=0.0001) and high dissimilarities (R=0.643) between fish communities in the two sections of Challawa River and also in Kano River (P=0.001, R=0.929). Analysis of Similarity Percentage indicated 74.45% of the dissmilarities between fish communities in the two sections were cummulatively contributed by four species in Challawa River and 72.18% by five species in Kano River. The distinct differences in fish abundance and richness between the two sections is ascribed to increased ecosytem productivity often associated with the inundated portion of dammed river. It is recommended that more water flow across the dams should be encouraged as a mitigating measure to boost basin sizes of the rivers at the below-dam sections. Key words: Diversity, dam, impound, reservoir, community, freshwater and fish species

On the Importance of Acidity in Cancer Cells and Therapy.

Cancer cells are associated with high glycolytic activity, which results in acidification of the tumor microenvironment. The occurrence of this stressful condition fosters tumor aggressiveness, with the outcome of invasiveness and metastasis that are linked to a poor clinical prognosis. Acidosis can be both the cause or consequence of alterations in the functions and expressions of transporters involved in intracellular acidity regulation. This review aims to explore the origin of acidity in cancer cells and the various mechanisms existing in tumors to resist, survive, or thrive in the acidic environment. It highlights the difficulties in measuring the intracellular pH evolution that impedes our understanding of the many regulatory and feedback mechanisms. It finally presents the consequences of acidity on tumor development as well as the friend or foe role of acidity in therapy.

Improvement of Hemoglobin Levels in Pregnant Women with Anemia Through Dragon Fruit Consumption

Anemia frequently manifests in pregnant women as a consequence of alterations in the cardiovascular system, leading to hemodilution and a subsequent decline in blood oxygen levels. The augmented iron demands during pregnancy arise from the needs of the fetus and placenta, coupled with physiological shifts like heightened blood volume and red blood cell count. This elevation in levels may contribute to diminished hemoglobin and hematocrit levels, consequently escalating the prevalence of anemia and iron deficiency during pregnancy. A viable solution for averting anemia in pregnant women involves the consumption of fruits rich in iron and vitamin C, such as dragon fruit, crucial for hemoglobin synthesis. The research method employed in this study followed a quantitative approach, specifically utilizing quasi-experimental research with a pretest-post-test design, including a control group. The study population comprised all pregnant women attending TPMB N Depok, West Java, during October-December 2023. Inclusion criteria involved pregnant women aged 16-34 weeks who visited TPMB N and exhibited signs of anemia. The study sample consisted of pregnant women willing to consume 200 cc of dragon fruit juice daily for a duration of 14 days. Bivariate data analysis was conducted using the Mann-Whitney Test. The intervention implemented involved administering dragon fruit juice, prepared by blending 200g of dragon fruit with 200cc of water and adding 3 tablespoons of sugar. The findings reveal a statistically significant difference in Hb levels among pregnant women before and after the consumption of dragon fruit juice, with a P value of 0.001.

Correlation of Microstructural Events with Stress Corrosion Cracking Initiation Behaviour in Additively Manufactured Ni-Based Alloy 718: Microcapillary Electrochemical Technique Implementation

During the past decade, metal additive manufacturing has gained tremendous attention for the production of substitutive components for oil, gas, and nuclear industries as a consequence of the possibility of fabricating complex full-density components with fewer manufacturing processes compared to conventional methods. Laser powder bed fusion (L-PBF) is one of the most precise additive manufacturing techniques based on layer-by-layer production of the final component with a high-power laser beam. Most investigations to dat focus on comparing the mechanical properties of additively manufactured components with conventional counterparts. Process parameter optimization has been extensively studied for obtaining almost full-density components with comparable and in some cases even better mechanical performance compared to conventionally manufactured components. However, the corrosion and more specifically stress corrosion cracking (SCC) behaviour of L-PBF and in general, additively manufactured components has received less attention. Since the major concern in critical industries is to reduce the risk of SCC occurrence, the mechanistic study of the effect of various micro and submicron structural alterations on SCC risk assessment is of paramount importance.It is well recognized in the corrosion community that the most critical stage of SCC is related to the incubation/initiation stage. From the information gathered by various authors in the past decades, having a prolonged incubation/initiation stage of SCC could significantly increase the lifetime of components, which results from the balance between the formation and destruction reactions occurring in the passive layer-environment interface. Thus, it is essentially always the case that by retarding the initiation of cracks, we significantly increase the life cycle. Until now, traditional electrochemical techniques are not able to detect the SCC initiation stage as a consequence of the large surface area in contact with the solution and the shortcomings of the used electrochemical techniques. Thus, during the past decades, extensive research has been done on the crack propagation stage by utilizing various techniques and statistical models for the prediction of crack growth rate. This study reports for the first time the correlation of electrochemical polarization behaviour with the susceptibility of the material to SCC initiation. Such an approach fulfils the knowledge gap covering the initiation mechanism by proposing the microcapillary method as the method of choice for mechanistic analysis of initiation susceptibility.In the current investigation, various electrochemical techniques combined with high-resolution microstructural analysis were implemented to elucidate the importance of submicron characteristics of L-PBF fabricated components on SCC initiation risk assessment. L-PBF fabricated Ni-Fe-Cr based alloy 718 with a slight variation of laser power in the range of achieving full density was used for elucidating the effect of slight alterations in micro and nanostructure in corrosion and SCC initiation behaviour. It was found that even with a slight variation of L-PBF process parameters such as laser power, various alterations occurred in micron and submicron scale namely, a slight decrease in hardness, an increase in subgrain width, porosity, dislocation density, the density of nanovoids adjacent to subgrain boundaries, and presence of carbide particles. Such alterations consequently lead to significant electrochemical behaviour and SCC initiation susceptibility. Furthermore, the underlying mechanisms responsible for the observed variations in SCC initiation susceptibility had been explained as a consequence of alterations in subgrain width, dislocation density, intrinsic nano cavities density adjacent to subgrain boundaries, and the presence of nanoscale carbide particles adjacent to subgrain boundaries. From the obtained results, the microcapillary technique proved to be a very useful and powerful tool for assessing SCC initiation susceptibility for additive manufactured components with submicron scale structures.

Deregulations of RNA Pol II Subunits in Cancer

Deregulated transcription is a well-known characteristic of cancer cells, with differentially expressed genes being a common feature of several cancers. Often, deregulated transcription is a consequence of alterations in transcription factors (TFs), which play a crucial role in gene expression and can act as tumour suppressors or proto-oncogenes. In eukaryotic organisms, transcription is carried out by three distinct RNA polymerase complexes: Pol I, Pol II, and Pol III. Pol II, specifically, is responsible for transcribing messenger RNA (mRNA), the protein coding part of the genome, as well as long non-coding RNAs (lncRNAs). While there is considerable research on the impact of specific deregulated transcription factors in cancer development, there is a lack of studies focusing on defects within the RNA polymerase complexes and their subunits. This review aims to shed light in particular on the Pol II complex and highlight the deregulation of its subunits that have a significant impact on tumour development, prognosis, and survival. By providing a comprehensive overview of our current understanding of Pol II subunits in cancer, this review emphasizes the importance of further research in this area. It suggests that exploring these subunits’ deregulations could lead to the identification of valuable biomarkers and potential therapeutic targets, making it a topic of collective interest.

Cognitive Impairment Is Associated with AMPAR Glutamatergic Dysfunction in a Mouse Model of Neuronal Methionine Synthase Deficiency.

Impairment of one-carbon metabolism during pregnancy, either due to nutritional deficiencies in B9 or B12 vitamins or caused by specific genetic defects, is often associated with neurological defects, including cognitive dysfunction that persists even after vitamin supplementation. Animal nutritional models do not allow for conclusions regarding the specific brain mechanisms that may be modulated by systemic compensations. Using the Cre-lox system associated to the neuronal promoter Thy1.2, a knock-out model for the methionine synthase specifically in the brain was generated. Our results on the neurobehavioral development of offspring show that the absence of methionine synthase did not lead to growth retardation, despite an effective reduction of both its expression and the methylation status in brain tissues. Behaviors were differently affected according to their functional outcome. Only temporary retardations were recorded in the acquisition of vegetative functions during the suckling period, compared to a dramatic reduction in cognitive performance after weaning. Investigation of the glutamatergic synapses in cognitive areas showed a reduction of AMPA receptors phosphorylation and clustering, indicating an epigenomic effect of the neuronal deficiency of methionine synthase on the reduction of glutamatergic synapses excitability. Altogether, our data indicate that cognitive impairment associated with methionine synthase deficiency may not only result from neurodevelopmental abnormalities, but may also be the consequence of alterations in functional plasticity of the brain.

Proopiomelanocortin (POMC) and psychodermatology.

Psychodermatology is the crossover discipline between Dermatology and Clinical Psychology and/or Psychiatry. It encompasses both Psychiatric diseases that present with cutaneous manifestations (such as delusional infestation) or more commonly, the psychiatric or psychological problems associated with skin disease, such as depression associated with psoriasis. These problems may be the result either of imbalance in or be the consequence of alteration in the homoeostatic endocrine mechanisms found in the systemic hypothalamic-pituitary-adrenal axis or in the local cutaneous corticotrophin-releasing factor-proopiomelanocortin-corticosteroid axis. Alteration in either of these systems can lead to immune disruption and worsening of immune dermatoses and vice-versa. These include diseases such as psoriasis, atopic eczema, acne, alopecia areata, vitiligo and melasma, all of which are known to be linked to stress. Similarly, stress and illnesses such as depression are linked with many immunodermatoses and may reflect alterations in the body's central and peripheral neuroendocrine stress pathways. It is important to consider issues pertaining to skin of colour, particularly with pigmentary disorders.

Trimethylamine N-Oxide as a Potential Risk Factor for Non-communicable Diseases: A Systematic Review.

Trimethylamine N-Oxide (TMAO), as a gut microbiota-derived metabolite, has been associated with a number of chronic diseases like cardiovascular diseases. Considering the increasing prevalence of non-communicable diseases (NCDs), we conducted a systematic review to discuss the TMAO association with NCDs. A comprehensive search has been conducted on PubMed, Web of Science, and Scopus databases up to December, 2020. The inclusion criteria were all related observational studies that surveyed the association between TMAO levels and non-communicable diseases. Interventional studies, animal experiments, reviews, case reports, letters, congress abstracts, and studies that were not published in English were excluded. Moreover, related review studies were separately discussed. Within 2191 recorded studies, 99 cross-sectional, case-control and cohort studies met the inclusion criteria. The most common diseases associated with TMAO levels are cardiovascular diseases, diabetes, kidney disease, stroke, inflammatory diseases, neurological disorders, and cancer. Elevated TMAO levels as a consequence of alteration in gut microbiota composition and dietary intake can lead to the incidence of NCDs. The high levels of TMAO can disrupt the homeostasis of glucose and lipids and induce inflammation that leads to serious NCDs. There is a dose-response relationship between TMAO levels and NCDs progression. Therefore, it can be studied as a therapeutic target or prognostic biomarker for dealing with NCDs.

Deepening Our Understanding of the Factors Affecting Landscape of Myeloproliferative Neoplasms: What Do We Know about Them?

Myeloproliferative neoplasms (MPNs) arise from the uncontrolled proliferation of hematopoietic stem and progenitor cells in bone marrow. As with all tumors, the development of MPNs is a consequence of alterations in malignant cells and their interaction with other extrinsic factors that support and promote tumor progression. Since the discovery of driver mutations, much work has focused on studying and reviewing the genomic features of the disease but has neglected to delve into the important role that many other mechanisms may play. This review discusses the genetic component of MPNs but focuses mainly on some of the most relevant work investigating other non-genetic factors that may be crucial for the disease. The studies summarized here address MPN cell-intrinsic or -extrinsic factors and the interaction between them through transcriptomic, proteomic and microbiota studies, among others.

The architecture and metabolic traits of monospecific photosynthetic biofilms studied in a custom flow-through system.

Microalgae biofilms have great ecological importance and high biotechnological potential. Nevertheless, an in-depth and combined structural (i.e., the architecture of the biofilm) and physiological characterization of microalgae biofilms is still missing. An approach able to provide the same time physiological and structural information during biofilm growth would be of paramount importance to understand these complex biological systems and to optimize their productivity. In this study, monospecific biofilms of a diatom and a green alga were grown under dynamic conditions in custom flow cells represented by UV/Vis spectroscopic cuvettes. Such flow cells were conceived to characterize the biofilms by several techniques mostly in situ and in a nondestructive way. Physiological traits were obtained by measuring variable chlorophyll a fluorescence by pulse amplitude modulated fluorometry and by scanning the biofilms in a spectrometer to obtain in vivo pigments spectral signatures. The architectural features were obtained by imaging the biofilms with a confocal laser scanning microscopy and an optical coherence tomography. Overall, this experimental setup allowed us to follow the growth of two biofilm-forming microalgae showing that cell physiology is more affected in complex biofilms likely as a consequence of alterations in local environmental conditions.

Differences in Immune Cell Mitochondrial Function in Black and White Patients with Heart Failure with Preserved Ejection Fraction

BACKGROUNDHeart failure with preserved ejection fraction (HFpEF) affects patients of all races and ethnicities. However, Black/African American patients are historically underrepresented in clinical research of HFpEF and have been reported to have unfavorable outcomes, yet the underlying mechanisms are not entirely understood. Excess proinflammatory cytokine and reactive oxygen species production from immune cells contributes to increased cardiovascular risk and may be a cause or consequence of alterations in immune cell metabolism. The aim of this study was to describe the immune cell bioenergetic profile in Black and White patients with HFpEF.METHODSWe studied 20 patients with HFpEF. 13 patients self‐reported as Black or African‐American (11 female; Median [IQR]: Age: 55 [50, 66] yrs; BMI 39 [36, 43] kg/m2; hsCRP 5.3 [3.5, 9.3] mg/dL; BNP 50 [50, 200] pg/mL) and 7 self‐reported as White (7 female; Age: 68 [43, 72] yrs; BMI 34 [33, 40] kg/m2; hsCRP 3 [1, 4.9] mg/dL; BNP 109 [50, 168] pg/mL). The mitochondrial bioenergetic profile was assessed in isolated peripheral blood mononuclear cells by a Seahorse XFp Analyzer. Respirometry coupled with modulators of cellular respiration were used to obtain basal respiration, ATP‐linked respiration, maximal respiration, proton linked respiration, spare respiratory capacity, and non‐mitochondrial respiration. The Mann Whitney U test was used to compare variables between groups.RESULTSProton leak respiration (Median [IQR]: 29 [4, 66] vs. 2.5 [1, 3] pmol/min, p=0.013), basal respiration 93 [60, 138] vs. 57 [53, 69] pmol/min, p = 0.008), maximal respiration (323 [191, 432] vs. 185 [162, 238] pmol/min, p = 0.0370) were higher in Black versus White patients. Raw spare respiratory capacity (232 [128, 293] vs. 125 [105, 145] pmol/min, p = 0.037) was also higher in Black versus White patients, whereas relative spare respiratory capacity (293% [276, 378] vs. 307% [259, 357] pmol/min, p=0.87) was not different between groups. There was a trend for lower coupling efficiency (94% [55, 95] vs. 97% [94, 99] pmol/min, p = 0.08) in Black vs White patients.CONCLUSIONIn an unselected cohort of patients with HFpEF, immune cell mitochondria basal respiration and respiratory reserve, as indicated by maximal respiration and spare respiratory capacity, are higher in Black versus White patients. Future studies are warranted to better understand the potential pathophysiological consequences of the observed differences.

Bone marrow transplantation induces changes in the gut microbiota that chronically increase the cytokine response pattern of splenocytes

Bone marrow transplantation (BMT) involves conditioning regimens which acutely induce side effects, including systemic inflammation, intestinal damage and shifts in the gut microbial composition, some of which may persist chronically. As the gut microbiota affect systemic immune responses, we aimed to investigate whether, post-BMT, the peripheral immune system is modulated as a direct consequence of alterations in the gut microbiota. We show that 24 weeks post-BMT, splenocytes but not peritoneal macrophages display increased cytokine response patterns upon ex-vivo stimulation with various pathogens as compared to untreated controls. The pattern of BMT-induced cytokine responses was transferred to splenocytes, and not to peritoneal macrophages, of healthy controls via co-housing and transferred to germfree mice via transplantation of cecum content. Thus, BMT induces changes in gut microbiota that in their turn increase cytokine responsiveness of splenocytes. Thus, BMT establishes a dominant microbiota that attenuates normalization of the immune-response.

Silver nanoparticles modify the hypothalamic-pituitary-interrenal axis and block cortisol response to an acute stress in zebrafish, Danio rerio.

The present study aimed at assessing the effects of exposure to silver nanoparticle (AgNP) and a subsequent acute stress on the expression of various genes involved in the hypothalamus-pituitary-interrenal (HPI) axis in zebrafish, Danio rerio. The fish were exposed to 0 (Control), 0.1 (LC), 0.4 (MC), and 1.2 (HC) mg Ag/L (as AgNP) over a 2-week period, followed by an acute air exposure stress. The whole body cortisol and the expression of selected genes in the fish brain and kidney were analyzed, before and after the acute stress. The results showed that AgNP increased basal cortisol levels and the expression of corticotropin releasing factor, prohormone convertase 1, pro-opiomelanocortin, and melanocortin 2 receptor; however, it suppressed/inhibited whole body cortisol, brain corticotropin releasing factor responses, pro-opiomelanocortin, and the kidney melanocortin 2 receptor responses to the acute stress. AgNP down-regulated the expression of the steroidogenic acute regulatory protein, but it intensified the gene expression in response to the acute stress. Before the acute stress, LC treatment exhibited an up-regulation in Cytochrome P450-11A-1 expression, but MC and HC treatments induced down-regulation. After the acute stress, the AgNP-exposed fish exhibited decreased Cytochrome P450-11A-1 expressions, compared with the Control. Exposure to AgNP significantly increased Cytochrome P450-11B expression. However, after the acute stress, LC treatment exhibited an up-regulation, but MC and HC treatments exhibited down-regulation in the Cytochrome P450-11B gene expression. In conclusion, AgNP suppressed cortisol response to stress, which appears to be a consequence of alterations in the HPI axis at the transcriptomic levels.

Utilisation of semiconductor sequencing for the detection of predictive biomarkers in glioblastoma.

The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival. The exponential increase in targeted agents directed at pivotal oncogenic pathways now provide new therapeutic opportunities for this tumour type. However, lack of comprehensive precision oncology testing at diagnosis means such therapeutic opportunities are potentially overlooked. To investigate the role of semiconductor sequencing for detection of predictive biomarkers in routine glioblastoma samples we have undertaken analysis of test trending data generated by a clinically validated next generation sequencing platform designed to capture actionable genomic variants distributed across 505 genes. Analysis was performed across a cohort of 55 glioblastoma patients. Analysis of trending data has revealed a complex and rich actionable mutational landscape in which 166 actionable mutations were detected across 36 genes linked to 17 off label targeted therapy protocols and 111 clinical trials. The majority of patients harboured three or more actionable mutations affecting key cancer related regulatory networks including the PI3K/AKT/MTOR and RAS/RAF/MEK/MAPK signalling pathways, DNA-damage repair pathways and cell cycle checkpoints. Linkage with immunotherapy and PARP inhibitors was identified in 44% of glioblastoma patients as a consequence of alterations in DNA-damage repair genes. Taken together our data indicates that precision oncology testing utilising semiconductor sequencing can be used to identify a broad therapeutic armamentarium of targeted therapies and immunotherapies that can be potentially employed for the improved clinical management of glioblastoma patients.

Transcriptomic and proteomic insights into patulin mycotoxin-induced cancer-like phenotypes in normal intestinal epithelial cells.

Patulin (PAT) is a natural contaminant of fruits (primarily apples) and their products. Significantly, high levels of contamination have been found in fruit juices all over the world. Several in vitro studies have demonstrated PAT's ability to alter intestinal structure and function. However, in real life, the probability of low dose long-term exposure to PAT to humans is significantly higher through contaminated food items. Thus, in the present study, we have exposed normal intestinal cells to non-toxic levels of PAT for 16weeks and observed that PAT had the ability to cause cancer-like properties in normal intestinal epithelial cells after chronic exposure. Here, our results showed that chronic exposure to low doses of PAT caused enhanced proliferation, migration and invasion ability, and the capability to grow in soft agar (anchorage independence). Moreover, an in vivo study showed the appearance of colonic aberrant crypt foci (ACFs) in PAT-exposed Wistar rats, which are well, establish markers for early colon cancer. Furthermore, as these neoplastic changes are consequences of alterations at the molecular level, here, we combined next-generation RNA sequencing with liquid chromatography mass spectrometry-based proteomic analysis to investigate the possible underlying mechanisms involved in PAT-induced neoplastic changes.

Vascular traits of stem galls: Cell increment versus morphogenetic constraints in wood anatomy.

Eremanthus erythropappus hosts globoid stem galls induced by Neolasioptera sp. (Diptera: Cecidomyiidae) close to the stem apex, which do not compromise the shoot apical meristem (SAM). We hypothesize that maintenance of the SAM, as well as the increasing number of leaves per branch and of galled stem lengths and diameters, are a consequence of alterations in vascular cells and, consequently, in the priority for water flow from non-galled stems to the stem galls. Our study focuses on the globoid stem galls to evaluate if gall induction and development promote changes in structure and function of secondary xylem cells. Anatomical, cytological, histometric and physiological methods were used to analyse non-galled stem branches (NGS), mature globoid stem galls and stem portions below and above the galls. These analyses revealed that vessel elements are larger in stem galls and in stem portions above the galls. Under Neolasioptera sp. induction activity, the vascular cambium of E. erythropappus produces less numerous but larger vessel elements and overproduces parenchyma cells. Contrary to the vascular constriction hypothesis proposed for bacterial galls, the vascular traits of the Neolasioptera sp. stem galls on E. erythropappus result in priority for water flow to galls and the non-galled portions above the galls, allowing the maintenance of galled stem growth and development.

Geochronological, geochemical and isotopic characterisation of the basement of the Chocó-Panamá Block in Colombia

The Chocó-Panamá block is the land bridge that connects Central and South America and forms the trailing edge of the Caribbean Large Igneous Province (CLIP). New field observations are combined with new geochemical, isotopic and 40Ar/39Ar analyses of the mafic basement of the Chocó block within Colombia. These are integrated with new U/Pb ages of detrital zircons extracted from siliciclastic and carbonate rocks that unconformably overlie the mafic basement. The data are used to constrain the age, tectonic origin and evolution of the Chocó Block, which are used to improve tectonic models of the Caribbean Plate. The whole-rock chemical and isotopic compositions of the mafic lavas suggests they formed within an oceanic plateau, and are extremely similar to plateau units in Colombia, Ecuador, Panamá and Costa Rica. 40Ar/39Ar (groundmass) dates of the mafic basement are affected by early calcic and late potassic alteration, and none are accurate measurements of the time of crystallisation. A comparison of 40Ar(radiogenic), 39Ar(K) and 37Ar(Ca) reveals at least three argon reservoirs within the mafic groundmass, where at least two are a consequence of alteration. Our most accurate albeit imprecise estimate of the crystallisation age of the mafic basement is ≥86.0 ± 6.3 Ma, which is a plateau 40Ar/39Ar date from a groundmass aliquot which contains the lowest proportion of secondary Ar reservoirs. This age estimate is consistent with the few reliable crystallisation ages obtained for oceanic plateau rocks of the CLIP. U/Pb concordia dates of detrital zircons constrain the maximum depositional age of the overlying sedimentary rocks to ~28 Ma, supporting previous conclusions that the Chocó-Panamá block collided with South America during the Oligocene to Early Miocene. Detrital Precambrian – Triassic zircons in the older cover sequences are not present in younger sedimentary rocks due to surface uplift of the Serranía del Baudó, presumably due to collisional tectonics.

Investigating Trends of Incidence Rates of Esophageal Cancer Divided by Squamous Cell Carcinoma and Adenocarcinoma in Southern Iran: a 10-Year Experience

Gastrointestinal cancers account for a significant number of deaths and new cancer cases worldwide. Our aim is to investigate stratum-specific incidence trends of esophageal cancer in southern Iran considering age, gender, and morphological (adenocarcinoma/squamous cell carcinoma) subtypes. We used data on esophageal cancer incidence in the catchment area of Shiraz Population-Based Cancer Registry. New cancer cases with ICD-O-3 codes of C15.0 to C15.9 were retrieved and prepared. New annual cases were counted for categories defied based on age group, gender, and morphology. Average annual percentage change (AAPC) and its 95% CI was estimated for each trend using joinpoint regression. The total number of esophageal cancer was higher in males than females. It is an increasing rate in esophageal adenocarcinoma in females and this increase was more prominent in older ages. Also, our study showed that SCC has a decreasing trend in females and a steady trend in males. Taken together, the increasing trend in adenocarcinoma in females in our study can be related to the increasing rate of obesity and smoking in females in recent years in our region. The incidence trend of different morphologic types of esophageal cancer is changing. This can be a consequence of alterations in the incidence trend of different risk factors. It is necessary to conduct more studies evaluating these risk factors.

Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer.

Simple SummaryComparative oncology is centered around the study of naturally occurring tumors in animals as a parallel and complementary model for human cancer research. Canine mammary tumors pose as excellent models since they share similarities in their spontaneous nature, histological subtypes, genetic background, and clinical course, which would be impossible to reproduce in murine models. Our study aimed to investigate cancer heterogeneity in primary tumors and metastasis, by applying bottom-up proteomics and mass spectrometry imaging to identify potential disease-state markers. We have demonstrated that the malignant phenotype may have arisen as a consequence of alterations in the expression of proteins involved in immune evasion facilitating metastatic events. To our knowledge, this is the first study to use mass spectrometry imaging in a dog model of breast cancer, that have demonstrated that poorly described proteins might play important roles in cancer spreading and should be further validated as potential early-stage tumor biomarkers.New insights into the underlying biological processes of breast cancer are needed for the development of improved markers and treatments. The complex nature of mammary cancer in dogs makes it a great model to study cancer biology since they present a high degree of tumor heterogeneity. In search of disease-state biomarkers candidates, we applied proteomic mass spectrometry imaging in order to simultaneously detect histopathological and molecular alterations whilst preserving morphological integrity, comparing peptide expression between intratumor populations in distinct levels of differentiation. Peptides assigned to FNDC1, A1BG, and double-matching keratins 18 and 19 presented a higher intensity in poorly differentiated regions. In contrast, we observed a lower intensity of peptides matching calnexin, PDIA3, and HSPA5 in poorly differentiated cells, which enriched for protein folding in the endoplasmic reticulum and antigen processing, assembly, and loading of class I MHC. Over-representation of collagen metabolism, coagulation cascade, extracellular matrix components, cadherin-binding and cell adhesion pathways also distinguished cell populations. Finally, an independent validation showed FNDC1, A1BG, PDIA3, HSPA5, and calnexin as significant prognostic markers for human breast cancer patients. Thus, through a spatially correlated characterization of spontaneous carcinomas, we described key proteins which can be further validated as potential prognostic biomarkers.