Biological Manifestations Research Articles

Hydroxyphenyl Butanone Induces Cell Cycle Arrest through Inhibition of GSK3β in Colorectal Cancer.

Background Colorectal cancer (CRC) is among the top three gastrointestinal malignancy in morbidity and mortality. The abnormal activation of Wnt/β-catenin pathway is considered to be a key factor in the occurrence and development of CRC. Novel inhibitor discovery against key factor in WNT pathway is important for CRC treatment and prevention. Methods Cell proliferation was detected after hydroxyphenyl butanone treatment in human colorectal cancer HCT116, LOVO, and normal colonic epithelial NCM460 cells. Colony formation, cell invasion ability, and cell cycle were detected with and without GSK-3β knockdown. Results Hydroxyphenyl butanone induces cycle arresting on G1-S phase of colorectal cancer cell line through GSK3β in Wnt/β-catenin pathway and inhibits malignant biological manifestations of cell proliferation, colony formation, and invasion. The inhibition in the high concentration group is stronger than that in the low concentration group, and the antitumor effect is different for different tumor cells. Under the same concentration of natural hydroxyphenyl butanone, the inhibition on normal colonic epithelial cells is significantly lower than that on tumor cells. The natural hydroxyphenyl butanone with medium and low concentration could promote the proliferation of normal colonic epithelial cells. Conclusion This study illustrated natural hydroxyphenyl butanone as new inhibitor of GSK3β and revealed the mechanisms underlying the inhibitory effects in colorectal cancer.

Effect of Exhaustive Training or Forced Immobilization on Physiological Condition and Main Metabolic and Stress Markers of Wistar Male Rats.

For correct and reliable experimental in vivo assessment of antistress effect of various bioactive substances, appropriate biomodels reproducing stress and organism response to stress in laboratory animals should be chosen. We chose treadmill test for simulating exhaustive physical load and forced immobilization accompanied by disorders of physiological and psychological condition. Verification of the models used indicates their wide applicability for testing certain biological manifestations under reproduced stress exposure.

Hypovitaminosis D in migrant children in Switzerland: a retrospective study

Cholecalciferol (vitamin D3) is essentially known for its role in the phosphocalcic metabolism and its associated pathologies, such as rickets. In Switzerland, 35 to 50% of children are vitamin D deficient. Due to skin colour, poor nutrition, living conditions and cultural practices, migrant population is particularly at risk. Our aim is to attest the prevalence of hypovitaminosis D in children arriving in Switzerland. We retrospectively assessed 528 children’s vitamin D status and parathyroid hormone, phosphate and calcium levels between 2015 and 2018 by electrochemiluminescence and spectrophotometry. Cholecalciferol was considered insufficient under 50 nmol/L and severely deficient below 25 nmol/L. Seventy-three percent of children showed hypovitaminosis D and 28% had a severe deficiency. Highest prevalence of deficiency was found in children from Eastern Mediterranean (80%) and African regions (75%). Severe deficiency was more prevalent in the South East Asian (39%) and Eastern Mediterranean regions (33%) and more frequent in females. Deficiency was more frequent and more severe in winter. Hypovitaminosis D increased with age. Two children presented with all three biological manifestations associated to severe hypovitaminosis D (hyperparathyroidism, hypocalcaemia and hypophosphatemia).Conclusion: A majority of migrant children presented with hypovitaminosis D. They should be supplemented to prevent complications. A strategy could be to supplement all children at arrival and during wintertime without regular vitamin D level checks.What is Known:Hypovitaminosis D is frequent in children and can lead to bone-related complications.Migrant children are particularly at risk of deficiency.What is New:Three-quarters of migrant children evaluated at our migrant clinic in Geneva’s children hospital are deficient in vitamin D, one third severely.A strategy to correct the deficiency would be to supplement all migrant children at arrival and in winter.

Characteristics and Developments in Mesenchymal Stem Cell Therapy for COVID-19: An Update.

The outbreak of coronavirus disease 2019 (COVID-19) has so far resulted in over a hundred million people being infected. COVID-19 poses a threat to human health around the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been confirmed as the pathogenic virus of COVID-19. SARS-CoV-2 belongs to the β-coronavirus family of viruses and is mainly transmitted through the respiratory tract. It has been proven that SARS-CoV-2 mainly targets angiotensin-converting enzyme II (ACE2) receptors on the surface of various cells in humans. The main clinical symptoms of COVID-19 include fever, cough, and severe acute respiratory distress syndrome (ARDS). Current evidence suggests that the damage caused by the virus may be closely related to the induction of cytokine storms in COVID-19. No specific drugs or measures have yet to be shown to cure COVID-19 completely. Cell-based approaches, primarily mesenchymal stem cells (MSCs), have been identified to have anti-inflammatory and immune functions in COVID-19. Clinical studies about using MSCs and its derivatives—exosomes for COVID-19 treatment—are under investigation. Here, we review the current progress of the biological characteristics, clinical manifestations, and cell-based treatment development for COVID-19. Providing up-to-date information on COVID-19 and potential MSC therapies will help highlight routes to prevent and treat the disease.

The Ethical Conundrums of “Precision Psychiatry”

The Ethical Conundrums of “Precision Psychiatry”

Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome.

Studies concerning the role of arachidonic acid (AA) and its metabolites in kidney disease are scarce, and this applies in particular to idiopathic nephrotic syndrome (INS). INS is one of the most frequent glomerular diseases in childhood; it is characterized by T-lymphocyte dysfunction, alterations of pro- and anti-coagulant factor levels, and increased platelet count and aggregation, leading to thrombophilia. AA and its metabolites are involved in several biological processes. Herein, we describe the main fields where they may play a significant role, particularly as it pertains to their effects on the kidney and the mechanisms underlying INS. AA and its metabolites influence cell membrane fluidity and permeability, modulate platelet activity and coagulation, regulate lymphocyte activity and inflammation, preserve the permeability of the glomerular barrier, influence podocyte physiology, and play a role in renal fibrosis. We also provide suggestions regarding dietary measures that are able to prevent an imbalance between arachidonic acid and its parental compound linoleic acid, in order to counteract the inflammatory state which characterizes numerous kidney diseases. On this basis, studies of AA in kidney disease appear as an important field to explore, with possible relevant results at the biological, dietary, and pharmacological level, in the final perspective for AA to modulate INS clinical manifestations.

The expression of THOX2 in colorectal mucinous adenocarcinoma and its relationship with prognosis.

e15529 Background: The role of THOX2 in the occurrence and development of tumors has gradually attracted attention, but there is no study on the expression and function of THOX2 in colorectal mucinous adenocarcinoma (MC). The purpose of this study was to investigate the expression of thyroid oxidase 2 (THOX2) in colorectal MC and its relationship with prognosis. Methods: 30 patients with colorectal adenocarcinoma (AC) and 15 patients with MC were selected from The Fourth hospital of Hebei Medical University from October 1, 2018 to July 1, 2019. They were selected to detect the mRNA and protein levels of THOX2 in the colorectal cancer tissues of the two different pathological types using qRT-PCR and immunohistochemistry (IHC) methods. A total of 109 patients with MC who received surgical treatment between January 1, 2015 and January 1, 2015 were selected. The clinicopathological parameters of the patients were collected and survival follow-up was performed. The expression of THOX2 protein in MC tissues was detected by IHC test, and the differences in the expression of THOX2 protein in different tissues were analyzed by χ2 test. Cox univariate and multivariate analyses were used to investigate the relationship between clinicopathological characteristics, THOX2 protein expression level and DFS and OS in patients with MC. Results: The levels of THOX2 mRNA and protein in 15 cases of MC were significantly higher than those in 30 cases of AC. The high expression of THOX2 protein in MC tissues was closely correlated with tumor site, whether mixed with other pathological types, TNM stage, lymph node metastasis, M stage, and liver metastasis, peritoneal metastasis and other site metastasis occurred in patients after initial treatment. Cox regression analysis of 95 patients' survival data showed that high expression of THOX2, right colon and lymph node metastasis were influential factors for DFS in MC patients, and were independent prognostic factors for predicting DFS in MC patients. The expression of THOX2, lymph node metastasis, liver metastasis after adjuvant therapy and peritoneal metastasis are the influencing factors of OS in MC patients. Lymph node metastasis is an independent prognostic factor for OS in MC patients. Conclusions: The expression of THOX2 in MC was significantly higher than that of AC, and it was related to the malignant biological manifestations of tumor. At the same time, the high expression of THOX2 is associated with short DFS and OS in patients with MC, and may be used as a potential biomarker and efficacy predictor for MC patients.

Results of isolated limb perfusion for metastasized malignant melanoma

Background and objectivesLocoregional metastases are typical biological manifestations of advanced malignant melanomas. Treatment with hyperthermic isolated limb perfusion (HILP) should be considered in affected patients. In the present study, we have analyzed the results of HILPs performed in our department. Patients and methodsEighty patients with locoregional metastases of the extremities received HILP at the Department of Surgery between January 2007 and December 2016. The mean follow-up was 38 months. ResultsThe study included 50 men and 30 women (mean age: 63 years). The median time between melanoma diagnosis and HILP was 25 months (range: 1–219 months). HILP was performed in curative (n = 45) and palliative (n = 35) intention. Seventy-five patients received a drug combination of melphalan/dactinomycin and five patients received a drug combination of melphalan/tumor necrosis factor-alpha. Remission rates were determined in 72 of 80 patients (90%) as follows: partial response n = 28, complete response n = 25, no response n = 19. Of the 25 patients with complete response, 13 patients developed a new tumor manifestation during follow-up (locoregional recurrences n = 4; distant metastases n = 3; both n = 6). The median overall survival rate was 33 months. Tumor stage influenced the survival rate significantly (p = 0.001). Patients with complete response showed a significantly better overall survival than patients with partial or no response (p = 0.016). ConclusionHILP is an effective therapeutic option in patients with locoregional metastases. This procedure carries a certain risk of side effects and adverse events but overall results in good response rates. Therefore, HILP should be offered to selected patients based on an individual discussion, considering their health status and oncological prognosis.

Pure red cell aplasia in systemic lupus erythematosus, a nationwide retrospective cohort and review of the literature.

To characterize the clinical and biological course, management and response to treatment in SLE-associated pure red cell aplasia (PRCA). This was a nationwide, multicentre, retrospective cohort study. From 2006 to 2018, we included adults with a diagnosis of PRCA supported by bone marrow examination and SLE or biologic manifestations of SLE after ruling out parvovirus B19 infection. We enrolled 24 patients (20 women). SLE was diagnosed before PRCA for 14 patients (median delay 81 months). At PRCA diagnosis, mean age, haemoglobin level, and reticulocyte and differential erythroblast count were 39.2 (13.2) years, 62 ( 20) g/l, 9.1 (7.6) × 109/l and 2.8 ( 2.5)%, respectively. Eleven (45%) patients experienced multiple PRCA flares (median 6, range 2-11). CS therapy resulted in only three complete sustained responses, and 19 (79%) patients required immunosuppressive agents with highly variable regimens. After a median follow-up of 76 months (range 13-173), 17 (71%) patients showed complete response for PRCA, 5 (21%) partial response and 2 (8%) treatment failure. In total, 21 (87%) patients required red blood cell transfusion; 5 had a diagnosis of transfusion-related iron overload. Eighteen (75%) patients experienced severe infectious events requiring hospitalization. SLE-associated PRCA is a severe condition. Repeated red blood cell transfusions and several lines of immunosuppressant therapy are mostly required, with high risk of severe infectious events and iron overload. Despite sustained response for PRCA and SLE obtained in most patients, the best therapeutic strategy remains to be determined.

Novel expert system to study human stress based on thermographic images

Human stress is a physical or emotional feeling. It can come from any situation or thought that makes one feel frustrated or nervous. Different biological manifestations take place in the presence of stress, such as tension, headache, and insomnia. Recent studies have reported that human stress can be related to facial expressions and fingertips due to temperature changes in the skin. Infrared thermography is a non-invasive technology that allows for the monitoring and analysis of human skin temperature. However, many works reported in the literature perform a manual analysis, depending on expert personnel, resulting in considerable human and economic efforts. In addition, the analyses reported to date with thermography are only based on the study of body parts. To reduce the limitations of these methodologies, expert systems have been proposed that simulate the thought process of a human expert to solve decision problems, which may be helpful for people focused on the health and psychology area who do not have expertise in the study of stress. Therefore, this paper proposes a novel expert system based on infrared thermography and thermal analysis of facial skin and fingertips, a rule-based method, and heuristic knowledge to classify and diagnose human stress in undergraduate university students. The system had the support of experts in the study of human stress and was validated in a stress study. The novel expert system was implemented in a local database that consisted of a group of 100 participants, undergraduate university students, of which 70 were stimulated by the Trier Social Stress Test (TSST) protocol and 30 were not induced to human stress, obtaining an accuracy in the expert system stress classification of 91.0%.

Renal Involvement and HBV Infection Are Common in Chinese Patients With Cryoglobulinemia.

Objectives: This study aimed to describe the main characteristics of Chinese patients with cryoglobulinemia, especially the characteristics of patients with different causes of cryoglobulinemia.Methods: Eighty inpatients diagnosed with cryoglobulinemia from different wards in Peking Union Medical College Hospital were included in this study. Demographic, clinical, biological, and renal pathological data were collected. We analyzed the characteristics of 61 patients with different causes of cryoglobulinemia.Results: Most patients (36/80, 45%) were diagnosed between 40 and 60 years of age. The male: female ratio was 1:1.5. Mixed (II + III) cryoglobulinemia accounted for the majority (43.8%) of cases. Renal involvement (87.5%), cutaneous involvement (57.5%), and fever (27.5%) were the most common clinical manifestations, while other manifestations included serositis and pulmonary and gastrointestinal involvement. The most common renal histopathological pattern was membranoproliferative glomerulonephritis (25/42, 59.5%). The secondary causes of cryoglobulinemia included infectious diseases (26/61, 32.5%), such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and connective tissue diseases (22/61, 27.5%), such as lupus and hematologic tumors (13/61, 16.3%). Patients with hematologic tumors were diagnosed at an older age (P = 0.044) and mostly had type I cryoglobulinemia (P < 0.001). No significant difference in clinical or biological manifestations was found among patients with different causes of cryoglobulinemia.Conclusions: This is the largest cohort of Chinese patients with cryoglobulinemia. We found that renal involvement and HBV infection might be more common in Chinese patients with cryoglobulinemia.

Факторы риска и молекулярные основы этиопатогенеза остеоартроза коленного сустава (обзор литературы)

Introduction Osteoarthritis (OA) is a heterogenic group of disorders of different etiology with similar biological, morphological and clinical manifestations and outcomes. OA is now considered a disease of the whole joint, including alterations in the articular cartilage, subchondral bone, synovial membrane, ligaments, capsule and periarticular muscles. OA of the knee as the most commonly affected joint accounts for the great medical, medical, social and economic impact. Material and methods A literature review assessing Russian and foreign studies on molecular mechanisms of etiology and pathogenesis of knee OA identified a set of factors for which there was consistent evidence for their association with onset of knee OA. A search of studies published in Russian and in English for the last ten years was conducted using bibliographic databases, including PubMed, PubMedCentral, GoogleScholar, eLIBRARY. Search terms included 'knee osteoarthritis', 'etiology', 'pathogenesis', 'risk factors'. Results Review of the literature showed that patients with knee OA are characterized by changes in cartilage, subchondral bone, synovium, suggesting common mechanisms of joint degeneration during OA development. Osteoarthritis (OA) is multifactorial in origin and closely associated with a wide spectrum of local (previous injury, muscle weakness, knee malalignment, knee surgeries, abnormal mechanical loading, excessive high impact sports, occupational physical activities) and systemic risk factors (advanced age, female sex, height, greater body mass index and obesity, hormone status, family history, mineral bone density, vitamin D deficiency, ethnicity). The prevalence of the knee OA and patterns of joint involvement vary among different racial and ethnic groups. Conclusion The literature review allowed us to identify the molecular mechanisms of etiopathogenesis of knee OA and the major risk factors for the pathology.

Diversity of non-palpable breast cancer. Timely diagnosis, adequate treatment and prevention

The goal. To show the variety of manifestations of non-palpablebreast cancer, which create difficulties in diagnostics and thechoice of treatment tactics, to focus on the need to accelerate theintroduction of the latest organ-saving treatment and diagnostictechnologies and prevention into the system of mammary cancerscreening. The main provisions. The epidemiology of cancer, riskfactors, positive trends in mammary cancer screening in Russia arepresented. A description is given of the diversity of X-ray sonographic and molecular biological manifestations of non-palpable breastcancer based on the results of the analysis of a complex clinicalX-ray sonographic pathomorphological and molecular geneticexamination of 1,212 patients with clinically latent breast diseases,including 708 patients with non-palpable cancer of various molecular subtypes, manifested by a variety of options – a nodulargrowth (40.1%), an accumulation of microcalcifications (17.5%), asite of local heavy rearrangement of the structure (31.2%), canceraccompanied by pathological secretion (6.6%), X-ray negativecancer (4.6%). When distributed by stages, 70.3% had T1N0M0, 25%had TisN0M0 and microinvasive cancer. For differential diagnosis,high-tech radiological techniques were used – 3D X-ray and ultrasound tomosynthesis. Effective preoperative diagnostics allowed foradequate organ-saving treatment, including oncoplastic surgery,high-power radiation therapy and modern targeted drug treatment,timely rehabilitation and prevention. Conclusion. Non-palpablebreast cancer has many faces. Knowledge of the variants of itsmanifestations and the use of modern diagnostic methods arenecessary for mammary cancer screening, which creates thepreconditions for adequate timely organ-saving treatment thatpreserves the life of patients and its quality.

Retrospective study of elderly onset sarcoidosis in Tunisian patients.

Background:Sarcoidosis is a systemic granulomatous disease of unknown etiology. It affects mostly young adults. In the elderly, the presentation of this disease is different, often posing positive diagnosis problems.Objectives:We intend to describe the various clinical features and the management of sarcoidosis in elderly patients (age ≥65 years) compared to the younger ones.Methods:We performed a retrospective, descriptive and comparative study in the Department of Internal Medicine in the University Hospital Hedi Chaker, Sfax, Tunisia, between 1996 and 2016.Results:From a series of 80 patients, we found sixteen patients (20%) with sarcoidosis diagnosed after the age of 65 years. A female preponderance (81,25%) was noted. Intrathoracic involvement concerned 13 patients (81,3%). Extrapulmonary signs were also frequent (93,8%). The main extrathoracic manifestations were ganglionar involvement (75%), an alteration of the general health (31,3%), hepatic involvement (31,3%), cutaneous involvement (25%) and ocular involvement (25%). Biological manifestations were hypercalcemia, hypercalciuria, lymphopenia and hypergammaglobulinemia noted in respectively 12,5%, 12,5%, 31,3% and 50% of the cases. Angiotensin-converting enzyme(ACE) level was elevated in 100% of the patients. Lymphadenopathy and cutaneous biopsies were important contributing factors to diagnosis (respectively: 100% and 75% were positive). Oral corticosteroid therapy was required in 50% of cases. Evolution was marked by pulmonary fibrosis in two cases. Satisfactory course of the disease was observed in the other patients.Conclusion:Young and elderly subjects had common characteristics of sarcoidosis, except for more coexisting chronic morbidities, no erythema nodosum and more frequent high levels of ACE in the elderly group.

Comparison between SARS-CoV and SARS-CoV 2

COVID-19, which is officially called SARS-CoV-2, is a newly emerging viral respiratory illness leading to a global epidemic, which causes concerns among the global community in November 2019. SARS-CoV-2 is considered as the third global coronavirus epidemic in the past 20 years after SARS-CoV in 2002 and MERS in 2012. SARS is a viral respiratory illness caused by coronavirus SARS-CoV which was first reported in Guangdong, China in 2002. SARS-CoV-2 and SARS-CoV share similar and different biological features, clinical manifestations, region distribution, transmission mechanisms, and clinical treatments. In this paper, differences and similarities between SARS-CoV-2 and SARS-CoV are analyzed to provide valuable information for further research. Through analysis, we found SARS-CoV-2 and SARSCoV share a lot of similarities, but also have differences in clinical manifestations, pathogenicity, transmission rate and treatments.

Phytoplankton characterisation in the Alappuzha mud banks during the pre-/post phases of a red-tide, Prorocentrum shikokuense Hada

The short-term changes in hydrochemical and phytoplankton characteristics occurring in the Alappuzha mud bank (AMB) region, located on the southwest coast of India, were monitored in association with a red-tide event caused by an autotrophic dinoflagellate, Prorocentrum shikokuense Hada. Dark-brownish waters detected in the AMB region on 7 September 2016, exhibited substantially high levels of chlorophyll a (68.29 mg m−3) and peridinin (53.61 mg m−3). The dominance of large-sized phytoplankton (>20μm), mostly of diatoms along with a moderate amount of fucoxanthin (>2.5 mg m−3), was detected in the study region during the pre-bloom period (10 and 28 August). The post-bloom period was characterised by the abundance of diatoms and dinoflagellates on 23 September, and cyanobacteria and diatoms on 14 October. The prevalence of cold (<25 ºC), nutrient-rich waters in the mud bank region indicated coastal upwelling from August. The extensive development of P. Shikokuense bloom in the mud bank region indicated the biological manifestation of upwelling induced nutrient enrichments. Because P.shikokuense Hada is recognised as a temperate water dinoflagellate species, its substantial blooming in a tropical regime such as Indian waters, especially on the southwest coast (Alappuzha coast), is highly concerning ecologically and societally.

A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-celllymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis.

Angioimmunoblastic T-cell lymphoma (AITL) is a uniquely aggressive mature T-cell neoplasm. In recent years, recurrent genetic mutations in ras homolog family member A (RHOA), tet methylcytosine dioxygenase 2 (TET2), DNA methyltransferase 3 alpha (DNMT3A) and isocitrate dehydrogenase [NADP(+)] 2 (IDH2) have been identified as associated with AITL. However, a deep molecular study assessing both DNA mutations and RNA expression profile combined with digital image analysis is lacking. The present study aimed to evaluate the significance of molecular and morphologic features by high resolution digital image analysis in several cases of AITL. To do so, a total of 18 separate tissues from 10 patients with AITL were collected and analyzed. The results identified recurrent mutations in RHOA, TET2, DNMT3A, and IDH2, and demonstrated increased DNA mutations in coding, promoter and CCCTC binding factor (CTCF) binding sites in RHOA mutated AITLs vs. RHOA non-mutated cases, as well as increased overall survival in RHOA mutated patients. In addition, single cell computational digital image analysis morphologically characterized RHOA mutated AITL cells as distinct from cells from RHOA mutation negative patients. Computational analysis of single cell morphological parameters revealed that RHOA mutated cells have decreased eccentricity (more circular) compared with RHOA non-mutated AITL cells. In conclusion, the results from the present study expand our understanding of AITL and demonstrate that there are specific cell biological and morphological manifestations of RHOA mutations in cases of AITL.

Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: differences in basic biology and treatment

In 2017 the World Health Organization revised the criteria for classification of pancreatic neuroendocrine neoplasms (pNENs) after a consensus conference at the International Agency for Research on Cancer. The major change in the new classification was to subclassify the original G3 group into well-differentiated pancreatic neuroendocrine tumors G3 (pNETs G3) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), which have been gradually proven to be completely different in biological behavior and clinical manifestations in recent years. In 2019 this major change subsequently extended to NENs involving the entire digestive tract. The updated version of the pNENs grading system marks a growing awareness of these heterogeneous tumors. This review discusses the clinicopathological, genetic and therapeutic features of poorly differentiated pNECs and compare them to those of well-differentiated pNETs G3. For pNETs G3 and pNECs (due to their lower incidence), there are still many problems to be investigated. Previous studies under the new grading classification also need to be reinterpreted. This review summarizes the relevant literature from the perspective of the differences between pNETs G3 and pNECs in order to deepen understanding of these diseases and discuss future research directions.

Production and Selection of Quality Protein Popcorn Hybrids Using a Novel Ranking System and Combining Ability Estimates.

Popcorn varieties are agronomically sub-optimal and genetically limited compared to other maize subspecies. To increase genetic diversity and improve popcorn agronomics, dent germplasm has been introduced to popcorn with limited success and generally, major loss of popping. Between 2013 and 2018, 12 Quality Protein Popcorn (QPP) inbreds containing Quality Protein Maize (QPM) and popcorn germplasm were produced that maintained popping while carrying the opaque-2 allele conferring elevated kernel lysine. This is an opportune trait in the growing market for healthier snacks and a model for mining QPM traits into popcorn. We crossed QPP inbreds to explore the effects of heterosis on popcorn protein, popping quality, and plant agronomics and selected hybrids for further production. To rank and intermediately prescreen hybrids, we utilized a novel hybrid-ranking model adapted from a rank summation index while examining the inbred general combining ability and hybrid specific combining ability estimates for all traits. We observed a biological manifestation of heterosis by categorizing hybrids by pedigree that resulted in a stepwise progression of trait improvement. These results corroborated our hybrid selection and offered insight in basic heterosis research. Estimates for popcorn quality and agronomic trait covariances also suggest the synergistic introgression of highly vitreous dent maize (QPM) into popcorn, providing a likely explanation for the successfully maintained vitreous endosperm, protein quality and popping traits in line with a remodeled proteome. QPP hybrids maintained improved amino acid profiles although different popping methods variably affected popcorn’s protein bound and free amino acid levels. This preliminary screening of QPP hybrids is enabling further quantitative selection for large-scale, complex trait comparison to currently marketed elite popcorn varieties.

TBL1XR1 Mutations in Primary Marginal Zone Lymphomas of Ocular Adnexa are Associated with Unique Morphometric Phenotypes

ABSTRACT Purpose Extranodal marginal zone B-cell lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT) that affects the ocular adnexa, also known as ocular adnexal MALT lymphomas (OAML), are low-grade lymphomas that mostly affect elderly individuals. This study was conducted to explore the genetic and microbial drivers of OMAL, and unique morphometric phenotypes associated with these mutations and infections. Materials and Methods In this study, we performed targeted deep sequencing of 8 OAML cases to identify its potential genetic and microbial drivers. We additionally performed computational digital image analysis of cases to determine if morphologic features corresponded to genetic mutations and disease biology. Results We identified TBL1XR1 as recurrently mutated in OAML (4/8), and mutations in several other oncogenes, tumor suppressors, transcription regulators, and chromatin remodeling genes. Morphologically, OAML cases with mutations in TBL1XR1 showed lymphoma cells with significantly lower circularity and solidity by computational digital image analysis (p-value <0.0001). Additionally, cases of OAML with mutations in TBL1XR1 showed equivalent or increased vascular density compared to cases without mutations in TBL1XR1. Finally, we did not find any infectious microbial organisms associated with OAML. Conclusions Our study showed recurrent mutations in TBL1XR1 are associated with unique morphometric phenotypes in OMAL cases. Additionally, mutations in genes associated with the methylation status of histone 3, nuclear factor (NF)-κB pathway, and NOTCH pathway were enriched in OMAL cases. Our findings have biologic and clinical implications as mutations in TBL1XR1 and other genes have the potential to be used as markers for the diagnosis of OAML, and also demonstrate a specific biologic phenotypic manifestation of TBL1XR1 mutations.