Miracle-dz/UniFAR-FTUs huggingface dataset:
Achiasmatic giant sex chromosomes in the vole Microtus cabrerae (Rodentia, Microtidae).

Conventional and microspread preparations of Microtus cabrerae spermatocytes were made to investigate the chromosomes of this species. Three different types of Y chromosomes, varying in size of the heterochromatic block, were observed; they were alike, however, in regard to synapsis, which was consistently absent. Our results suggest that the heterochromatic blocks are not involved in the lack of synapsis and that asynapsis is a cytological feature common to all species of the family Microtidae. In addition, the co-aligned configuration of the ends of the sex-chromosome axes of this species and the lack of silver-stainable threads or filaments connecting them suggest the existence of two mechanisms for association of the sex chromosomes during prophase I and metaphase I: attachment of the ends of both sex chromosome axes to the nuclear envelope and heterochromatin "stickiness. "
A high preoperative carbohydrate antigen 19-9 level is a risk factor for recurrence in stage II colorectal cancer

Abstract Background: Many risk factors for recurrence in stage II colorectal cancer (CRC) have been proposed, and the efficacy of adjuvant chemotherapy is still controversial. This study aimed to identify risk factors for tumor recurrence and assess whether they are related to the benefits of adjuvant chemotherapy in stage II CRC. Material and methods: Patients with stage II CRC that was curatively operated on in a tertiary hospital between 2005 and 2014 were analyzed. Cox’s proportional hazards models were applied to identify risk factors for recurrence and overall mortality. Kaplan-Meier methods were used to evaluate whether adjuvant chemotherapy was beneficial in terms of recurrence-free survival (RFS). Results: A total of 384 patients were identified, among whom 38 (10%) received adjuvant chemotherapy. In a median follow-up of 48.6 months, 52 patients (14%) developed recurrence. Multivariate analyses identified two independent parameters that significantly decreased RFS; pathological T4 [hazard ratio (HR), 2.34; 95% confidence interval (CI), 1.31–4.15; p = . 0045) and preoperative carbohydrate antigen (CA) 19-9 > 37 U/ml (HR 1.96; 95% CI 1.02–3.58; p = .045). These factors also inversely correlated with overall survival; T4: HR 2.10, p = . 019) and CA 19-9 > 37 U/ml (HR 2.15, p = .025). The combination of T4 and CA 19-9 > 37 U/ml resulted in an increased HR (3.52) for recurrence. However, adjuvant chemotherapy did not improve RFS in patients with these features. Conclusion: The present study demonstrated elevated CA 19-9 levels as well as T4 independently predicted worse long-term outcomes in patients with stage II CRC. However, the characterization of patients who gain survival advantages by adjuvant chemotherapy requires further investigation.
Ibuprofen and diclofenac treatments reduce proliferation of pancreatic acinar cells upon inflammatory injury and mitogenic stimulation

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are administered to manage the pain typically found in patients suffering from pancreatitis. NSAIDs also display anti‐proliferative activity against cancer cells; however, their effects on normal, untransformed cells are poorly understood. Here, we evaluated whether NSAIDs inhibit the proliferation of pancreatic acinar cells during the development of acute pancreatitis.
Factor Xa and Prothrombin: Mechanism of Action of FEIBA

A complex consisting of activated factor X (FX) (enzyme) and prothrombin (substrate), both highly purified from human plasma and virus inactivated, was formulated, characterised biochemically as well as in animal studies, and given the name Partial Prothrombinase (PPT). In vitro, PPT shortened the clotting time of a high–titre human factor VIII (FVIII) inhibitor plasma in a manner similar to that of the activated prothrombin complex concentrate FEIBA and triggered coagulation in plasma samples in which factor V (FV) is present. In vivo, the ability of PPT to activate coagulation in both chimpanzees and baboons was equivalent to that of FEIBA. PPT also triggered coagulation in a von Willebrand factor(vWF)–deficient dog and controlled bleeding in rabbits with antibody–induced haemophilia A. Thus, studying the mechanism of action of PPT also explains the therapeutic principle of FEIBA.
BNIP3L in myelodysplastic syndromes and acute myeloid leukemia: impact on disease outcome and cellular response to decitabine

Changes in apoptosis of hematopoietic progenitors are thought to contribute to the progression of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). [1][1] BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and BNIP3-like (BNIP3L) are closely related members of the BCL2 family of
Seven-day human biological rhythms: An expedition in search of their origin, synchronization, functional advantage, adaptive value and clinical relevance

ABSTRACT This fact-finding expedition explores the perspectives and knowledge of the origin and functional relevance of the 7 d domain of the biological time structure, with special reference to human beings. These biological rhythms are displayed at various levels of organization in diverse species – from the unicellular sea algae of Acetabularia and Goniaulax to plants, insects, fish, birds and mammals, including man – under natural as well as artificial, i.e. constant, environmental conditions. Nonetheless, very little is known about their derivation, functional advantage, adaptive value, synchronization and potential clinical relevance. About 7 d cosmic cycles are seemingly too weak, and the 6 d work/1 d rest week commanded from G-d through the Laws of Mosses to the Hebrews is too recent an event to be the origin in humans. Moreover, human and insect studies conducted under controlled constant conditions devoid of environmental, social and other time cues report the persistence of 7 d rhythms, but with a slightly different (free-running) period (τ), indicating their source is endogenous. Yet, a series of human and laboratory rodent studies reveal certain mainly non-cyclic exogenous events can trigger 7 d rhythm-like phenomena. However, it is unknown whether such triggers unmask, amplify and/or synchronize previous non-overtly expressed oscillations. Circadian (~24 h), circa-monthly (~30 d) and circannual (~1 y) rhythms are viewed as genetically based features of life forms that during evolution conferred significant functional advantage to individual organisms and survival value to species. No such advantages are apparent for endogenous 7 d rhythms, raising several questions: What is the significance of the 7 d activity/rest cycle, i.e. week, storied in the Book of Genesis and adopted by the Hebrews and thereafter the residents of nearby Mediterranean countries and ultimately the world? Why do humans require 1 d off per 7 d span? Do 7 d rhythms bestow functional advantage to organisms? Is the magic ascribed to the number 7 of relevance? We hypothesize the 7 d time structure of human beings is endogenous in origin – a hypothesis that is affirmed by a wide array of evidence – and synchronized by sociocultural factors linked to the Saturday (Hebrews) or Sunday (Christian) holy day of rest. We also hypothesize they are representative, at least in part, of the biological requirement for rest and repair 1 d each 7 d, just as the circadian time structure is representative, in part, of the biological need for rest and repair each 24 h.
Regulation of the expression of cyclic GMP-dependent protein kinase by cell density in vascular smooth muscle cells.

Cyclic GMP-dependent protein kinase (cGMP kinase) is the major receptor protein for cGMP in vascular smooth muscle. Vascular smooth muscle cells (VSMC) isolated from the rat aorta express type I cGMP kinase at high levels, but expression decreases markedly upon passage of the cells. In primary or early passage, the expression of cGMP kinase is lowest when cells are plated at low density as assessed by immunological and Northern analyses. Expression increases at confluence and is maintained in postconfluent cultures. With repeated passaging, however, the levels of cGMP kinase decrease even in confluent and postconfluent cultures so that after several passages enzyme levels are undetectable. The decrease in expression in passaged cells is not due to exposure to serum-derived growth factors, but rather on the repeated exposure of cells to conditions in which cell density is reduced (i.e., subculturing). These results indicate that aortic VSMC grown at low density or those repetitively passaged have reduced expression of cGMP kinase, and thus may not represent appropriate cultures with which to investigate the role of nitric oxide and cGMP in VSMC function.
Optical limiting performance of a GaAs/AlAs heterostructure microcavity in the near-infrared.

A multilayer GaAs/AlAs heterostructure forming a Fabry-Perot microcavity with a narrow resonance at 1.1 μm was produced by molecular-beam epitaxy. Under nanosecond pulsed laser radiation, a blueshift of the resonant line, associated with a photo-induced negative change in refractive index in GaAs, was experimentally registered by using an optical parametric oscillator. The spectral shift was accompanied by a reduction in peak transmittance, associated with nonlinear intracavity absorption. Such a cavity can be used as an optical limiter at the resonant wavelength when both the spectral shift and the transmittance reduction contribute to the limiting effect. An exceptionally low limiting threshold of about 1 mJ/cm2 was observed in the experiment.
A Systemic Review of Transoral Thyroidectomy

Background: Transoral thyroidectomy is a kind of “natural orifice transluminal endoscopic surgery (NOTES)” which is now being performed in increasing frequency. However, the safety and feasibility have not been concluded yet. Materials and Methods: A systemic literature search was performed in Pubmed, Cochrane, and Embase databases to identify all studies written in English and published up to April 2017. The keywords used were “transoral endoscopic,” “transoral robotic,” “oral vestibular endoscopic,” and “oral vestibular robotic” combined with “thyroidectomy” or “thyroid surgery. ” Results: Ten articles containing 211 cases matched the review criteria. The weighted average operative time was 119.9 minutes with an average intraoperative blood loss of 35.5 mL while the weighted average length of hospital stay was 4.0 days. The overall conversion rate to open surgery was 1.9%. An overall incidence rate of temporary hypoparathyroidism was 7.1%, temporary recurrent laryngeal nerve injury was 4.3%, whereas of mental nerve palsy was 4.3%. Conclusions: According to those reviewed literatures, we can conclude that transoral thyroidectomy is safe and feasible in well-selected patients and offers good perioperative and postoperative outcomes.
Editorial: sofosbuvir plus daclatasvir for the treatment of hepatitis C—can one size fit all?

ment of complications (Figure 1). In view of these results, experimental studies assessing the immunophenotype and function of monocytes/macrophages would be interesting, in order to confirm the source of increased levels of sCD163 and sMR in patients with cirrhosis and its relationship with immune cell function. Finally, whether modulating the monocyte/macrophage population function in patients with cirrhosis may be a promising therapeutic target will have to be evaluated in future studies.
The Role of Marital Status in Physical Activity Among African American and White Men

Racial differences in physical activity among men are well documented; however, little is known about the impact of marital status on this relationship. Data from the National Health and Examination Survey (NHANES) 1999-2006 was used to determine whether the association of race and physical activity among men varied by marital status. Marital status was divided into two categories: married and unmarried. Physical activity was determined by the number of minutes per week a respondent engaged in household/yard work, moderate and vigorous activity, or transportation (bicycling and walking) over the past 30 days. The sample included 7,131 African American (29%) and White(71%) men aged 18 years and older. All models were estimated using logistic regression. Because the interaction term of race and marital status was statistically significant (p < .001), the relationship between race, physical activity, and marital status was examined using a variable that reflects the different levels of the interaction term. After adjusting for age, income, education, weight status, smoking status, and self-rated health, African American married men had lower odds (odds ratio = 0.53, 95% confidence interval = [0.46-0.61], p < .001) of meeting federal physical activity guidelines compared with White married men. Possible dissimilarities in financial and social responsibilities may contribute to the racial differences observed in physical activity among African American and White married men.
Expression of the Tyrosine Kinase Activity Growth Factor Receptors (EGFR, ERB B2, ERB B3) in Colorectal Adenocarcinomas and Adenomas

The overexpression of three growth factor receptors: epidermal growth factor receptor (EGFR), ERB B2 and ERB B3 was evaluated immunohistochemically in 77 malignant and 15 benign colorectal neoplasms considering clinicopathological variables (histological structure, grade of differentiation, tumor localization, clinical stage of the disease). The relationship between the coexpression of EGFR-related proteins in individual patients was also evaluated. EGFR expression was revealed in comparable percentages of colorectal adenoma and in adenocarcinoma cases (80% and 70%) while ERB B2 expression was detectable more frequently in adenoma than in adenocarcinoma cases (87% and 54%). The presence of ERB B3 was observed in a higher percentage of adenocarcinoma than adenoma cases (65% and 40%). There was no correlation between the expression of studied tyrosine kinase receptors and histological grade or Dukes’ clinical stage and localization (proximal or distal) of colorectal adenocarcinoma. The incidence of EGFR and ERB B2 expression was higher in tubulovillous (100% for both receptors) than in tubular adenomas (63% and 75%), while the ERB B3 receptor was revealed more frequently in tubular than in tubulovillous neoplasms (50% and 28%). These differences appeared to be statistically nonsignificant. The concomitant expression of two growth factor receptors was observed in a higher percentage of colorectal adenomas than adenocarcinomas, and the coexistence of three growth factors was revealed in comparable percentages in malignant and benign colorectal tumors. Our results support the promotional rather than direct transformational role for the EGFR supergene family in colorectal tumorigenesis. The frequently observed coexpression of more than one EGFR-related protein in colorectal neoplasms indicates the possible cooperation of these receptors in mitogenic signaling transduction, facilitating the development and maintenance of the malignant phenotype.
Sickle Cell Trait Prevalence Among U.S. Military Service Members: 1992-2012.

BACKGROUND Population-based estimates of sickle cell trait (SCT) prevalence in the U.S. military across services and over time are lacking. METHODS SCT prevalence by service, race/ethnicity, and gender in 5-year time intervals was estimated using demographic, ambulatory, and hospital SCT encounter (International Classification of Diseases, 9th Revision, Clinical Modification 282.5) data for active duty, enlisted between 1992 and 2012 and limited SCT laboratory results. RESULTS Our study identified 15,081 SCT subjects. SCT prevalence varied significantly by race, year, gender, and service branch. SCT prevalence was highest for non-Hispanic blacks (5.02%; prevalence ratio = 56.33, confidence interval [CI] = 52.14-60.85; compared to non-Hispanic white) in 2005-2009 (0.40%; prevalence ratio = 10.04, CI = 9.21-10.94; compared to 1992-1994), for women (2.97%; prevalence ratio = 3.14, CI = 3.04-3.25; compared to men), and in the Navy (2.26%; prevalence ratio = 2.96, CI = 2.84-3.02; compared to Army). Among foreign born, Africans were more likely to be SCT+ (prevalence ratio = 1.68, CI = 1.39-2.04; compared to non-U.S. North American). CONCLUSION This study estimated the prevalence of SCT within U.S. military enlisted force and describes variability across services for race, time intervals, gender, and foreign-born region and will support investigation into the health effects of SCT in young adult populations.
Mechanism and dynamics of INPP5E transport into and inside the ciliary compartment

Abstract The inositol polyphosphate 5′-phosphatase E (INPP5E) localizes to cilia. We showed that the carrier protein phosphodiesterase 6 delta subunit (PDE6δ) mediates the sorting of farnesylated INPP5E into cilia due to high affinity binding and release by the ADP-ribosylation factor (Arf)-like protein Arl3·GTP. However, the dynamics of INPP5E transport into and inside the ciliary compartment are not fully understood. Here, we investigate the movement of INPP5E using live cell fluorescence microscopy and fluorescence recovery after photobleaching (FRAP) analysis. We show that PDE6δ and the dynein transport system are essential for ciliary sorting and entry of INPP5E. However, its innerciliary transport is regulated solely by the intraflagellar transport (IFT) system, independent from PDE6δ activity and INPP5E farnesylation. By contrast, movement of Arl3 into and within cilia occurs freely by diffusion and IFT-independently. The farnesylation defective INPP5E CaaX box mutant loses the exclusive ciliary localization. The accumulation of this mutant at centrioles after photobleaching suggests an affinity trap mechanism for ciliary entry, that in case of the wild type is overcome by the interaction with PDE6δ. Collectively, we postulate a three-step mechanism regulating ciliary localization of INPP5E, consisting of farnesylation- and PDE6δ-mediated targeting, INPP5E-PDE6δ complex diffusion into the cilium with transfer to the IFT system, and retention inside cilia.
The Awá-Guajá Indians of the Brazilian Amazon

The South-American Indian group Awá-Guajá, currently living in the State of Maranhão (Northeastern Brazil), is one of the most recently contacted Indian groups of the Brazilian Amazon. This group is made up by three partially isolated villages named Awá, Guajá and Juriti, and is characterized by having a young population, in which 47.6% of the individuals range from 0 to 14 years old. The sex ratios (male/female) for people of reproductive age are 1.13 for Awá village, 2.00 for Guajá, 3.33 for Juriti and 1.61 for the tribe as a whole. Fst and heterogeneity analysis show that, despite the small differences observed among villages for the eight genetic systems analyzed, the Awá-Guajá tribe is constituted of only one population. Furthermore, comparisons between Awá-Guajá and Urubú-Kaapor tribes indicate that they are still isolated genetically, in spite of the fact that they share territories.
α-Conotoxin ImI-modified polymeric micelles as potential nanocarriers for targeted docetaxel delivery to α7-nAChR overexpressed non-small cell lung cancer

Abstract A micelle system modified with α-Conotoxin ImI (ImI), a potently antagonist for alpha7 nicotinic acetylcholine receptor (α7-nAChR) previously utilized for targeting breast cancer, was constructed. Its targeting efficiency and cytotoxicity against non-small cell lung cancer (NSCLC) highly expressing α7-nAChR was investigated. A549, a non-small cell lung cancer cell line, was selected as the cell model. The cellular uptake study showed that the optimal modification ratio of ImI on micelle surface was 5% and ImI-modification increased intracellular delivery efficiency to A549 cells via receptor-mediated endocytosis. Intracellular Ca2+ transient assay demonstrated that ImI modification led to enhanced molecular interaction between nanocarriers and A549 cells. The in vivo near-infrared fluorescence imaging further revealed that ImI-modified micelles could facilitate the drug accumulation in tumor sites compared with non-modified micelles via α7-nAChR mediation. Moreover, docetaxel (DTX) was loaded in ImI-modified nanomedicines to evaluate its in vitro cytotoxicity. As a result, DTX-loaded ImI-PMs exhibited greater anti-proliferation effect on A549 cells compared with non-modified micelles. Generally, our study proved that ImI-modified micelles had targeting ability to NSCLC in addition to breast cancer and it may provide a promising strategy to deliver drugs to NSCLC overexpressing α7-nAChR.
Handedness in gestural and manipulative actions in male hunter-gatherer Aka pygmies from Central African Republic.

OBJECTIVES All human populations display a right-biased handedness. Nonetheless, if studies on western populations are plenty, investigations of traditional populations living at subsistence levels are rare. Yet, understanding the geographical variation of phenotypes of handedness is crucial for testing evolutionary hypotheses. We aimed to provide a preliminary investigation of factors affecting handedness in 25 Aka pygmies from Central African Republic when spontaneously gesturing or manipulating food/tools (Nactions = 593). MATERIALS AND METHODS We recorded spontaneous behaviors and characterized individuals' hand preference using GLMM with descriptive variables as target position, task complexity (unimanual/bimanual), task nature (food/tool manipulation, gesture), and task physical/cognitive constraints (precision or power for manipulative actions and informative content for gestures). RESULTS Individuals were lateralized to the right (93%, N = 15) when manipulating food/tools but not when gesturing. Hand preference was affected by target position but not by task complexity. While nonexplicitly informative gestures were more biased to the right compared to explicitly informative ones, no differences were found within food/tool manipulation (power or precision vs. none). DISCUSSION Although we do not intend to assume generalizable results due to our reduced sample, our observations provide additional information on handedness in a contemporary traditional society. Especially, the study mainly evidenced considerable cultural effects in gestures while also supporting theories considering active tool manipulation as one of the overriding factor in human handedness evolution.