Miracle-dz/UniFAR-FTUs huggingface dataset:
Podocarp Evolution: A Molecular Phylogenetic Perspective

Phylogenetic reconstructions of the relationships among extant taxa can be used to infer the nature of the processes that have generated contemporary patterns of biotic diversity. In this study, we present a molecular phylogenetic hypothesis for the conifer family Podocarpaceae based upon three DNA fragments that have been sampled for approximately 90 taxa. We use Bayesian relaxed- clock methods and four fossil con - straints to estimate divergence times among the lineages of Podocarpaceae. Our dating analyses suggest that although the family is old (Triassic�Jurassic), the extant species groups are of recent evolutionary origin (mid- to late Cenozoic), a pattern that could reflect a temporal increase in the rate lineage accumulation or, alternatively, a high and constant rate of extinction. Our data do not support the hypothesis that Podocarpaceae have diversified at a homogeneous rate, instead providing strong evidence for a three- to eightfold increase in diversification associated with the Podocarpoid� Dacrydioid clade, which radiated in the mid- to late Cretaceous to the earliest Cenozoic, around 60�94 mya . This group includes a predominance of taxa that develop broad leaves and/or leaf - like shoots and are distributed predominantly throughout the tropics. Tropical podocarps with broad leaves may have experienced reduced extinction and/or increased speciation coincident with the radiation of the angiosperms, the expansion of megathermal forests, and relatively stable tropical climates that were widespread through the Tertiary
Midgap radiative centers in carbon-enriched hexagonal boron nitride

Significance Well‐defined defect centers play a crucial role in condensed-matter physics. That is particularly evident in the case of semiconductors and wide‐gap insulators, where midgap levels provide a number of versatile functionalities: from lasing to pressure sensing. Individual defects may become single-photon sources—crucial for applications in quantum technology. Recently, such defects have been observed in hexagonal boron nitride (hBN). Here, a method to fabricate stable and reproducible defects in hBN is introduced. Large bandgap of boron nitride allows the use of such defects in many quantum applications. Fabrication and characterization of such defects in hBN, which has become a relevant, emerging, wide-bandgap 2D material, is an important step toward novel functionalities of van der Waals heterostructures. When serving as a protection tissue and/or inducing a periodic lateral modulation for/in atomically thin crystals, hexagonal boron nitride (hBN) has revolutionized the research on van der Waals heterostructures. By itself, hBN appears as an emergent wide-bandgap material, which, importantly, can be optically bright in the far-ultraviolet range and which frequently displays midgap defect-related centers of yet-unclear origin, but, interestingly, acting as single-photon emitters. Controlling the hBN doping is of particular interest in view of the possible practical use of this material. Here, we demonstrate that enriching hBN with carbon (C) activates an optical response of this material in the form of a series of well-defined resonances in visible and near-infrared regions, which appear in the luminescence spectra measured under below-bandgap excitation. Two, qualitatively different, C-related radiative centers are identified: One follows the Franck–Condon principle that describes transitions between two defect states with emission/annihilation of optical phonons, and the other shows atomic-like resonances characteristic of intradefect transitions. With a detailed characterization of the energy structure and emission dynamics of these radiative centers, we contribute to the development of controlled doping of hBN with midgap centers.
Thrombopoietin is required for full phenotype expression in a JAK2V617F transgenic mouse model of polycythemia vera

The myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis and primary myelofibrosis are hematopoietic stem cell disorders and share driver mutations that either directly activate the thrombopoietin receptor, MPL, or activate it indirectly through gain-of-function mutations in the gene for JAK2, its cognate tyrosine kinase. Paradoxically, MPL surface expression in hematopoietic stem cells is also reduced in the myeloproliferative neoplasms due to abnormal post-translational glycosylation and premature destruction of JAK2, suggesting that the myeloproliferative neoplasms are disorders of MPL processing since MPL is the only hematopoietic growth factor receptor in hematopoietic stem cells. To examine this possibility, we genetically manipulated MPL expression and maturation in a JAK2V617F transgenic mouse model of polycythemia vera. Elimination of MPL expression completely abrogated the polycythemia vera phenotype in this JAK2V617F transgenic mouse model, which could only be partially restored by expression of one MPL allele. Most importantly, elimination of thrombopoietin gene expression abrogated the polycythemia vera phenotype in this JAK2V617F transgenic mouse model, which could be completely restored by expression of a single thrombopoietin allele. These data indicate that polycythemia vera is in part a thrombopoietin-dependent disorder and that targeting the MPL-thrombopoietin axis could be an effective, nonmyelotoxic therapeutic strategy in this disorder.
Novel Fredericamycin Variant Overproduced by a Streptomycin-Resistant Streptomyces albus subsp. chlorinus Strain

Streptomycetes are an important source of natural products potentially applicable in the pharmaceutical industry. Many of these drugs are secondary metabolites whose biosynthetic genes are very often poorly expressed under laboratory cultivation conditions. In many cases, antibiotic-resistant mutants exhibit increased production of natural drugs, which facilitates the identification and isolation of new substances. In this study, we report the induction of a type II polyketide synthase gene cluster in the marine strain Streptomyces albus subsp. chlorinus through the selection of streptomycin-resistant mutants, resulting in overproduction of the novel compound fredericamycin C2 (1). Fredericamycin C2 (1) is structurally related to the potent antitumor drug lead fredericamycin A.
Quantitative Estimate of Weeds of Sugarcane ( Saccharum Officinarum L.) Crop in Ilorin, Southern Guinea Savanna of Nigeria

A survey was conducted in the sugarcane fields of Unilorin Sugar Research Institute, Ilorin in the southern Guinea savanna agro-ecological zone of Nigeria during 2011 and 2012 cropping seasons with an objective to identify the current status of prevalent weeds in rainfed and irrigated sugarcane fields. A quantitative method was employed for the enumeration of weeds. Quadrats were laid along transects and individual weed species in each quadrat was identified and counted. Simpson’s diversity index, Sorensen similarity index and relative abundance were used to determine the weed community structure. A total of 51 weed species belonging to 40 genera within 16 families were identified across the sugarcane fields. Rainfed sugarcane field was higher in weed species (41) than irrigated fields (35 weed species). Rainfed fields also had the diversity index of 28.84 % compared to 21.66% species diversity computed for irrigated fields. The result generally shows that the similarities index of weed species between rainfed and irrigated fields is about 50 %. Among the 10 abundant weed species, two grasses viz. Panicum repens L. and Imperata cylindrica (L.) Raeschel were the most abundant weeds in sugarcane fields followed by Rottboellia cochinchinensis Lour and two sedge weeds Cyperus rotundus L. and Mariscus longibracteatus Cherm . Results obtained from this study would be useful in creating a weed management programme and making informed decision on choice of herbicides. Regular weed survey to identify possible problematic weeds and weed population shifts and direct research toward new or improved weed control measures is thereby recommended. Key words : Sugarcane fields, rainfed, irrigation, survey, weed species
Estrogen-induced epigenetic silencing of FTH1 and TFRC genes reduces liver cancer cell growth and survival

ABSTRACT Estrogen (E2) regulates hundreds of genes involved in cell metabolism and disrupts iron homoeostasis in various cell types. Herein, we addressed whether E2-induced epigenetic modifications are involved in modulating the expression of iron-regulatory genes. Epigenetic status of FTH1 and TFRC genes was assessed in E2-treated cancer cells. E2-induced DNA methylation was associated with decreased FTH1 and TFRC expression in Hep-G2 and Huh7 cells, but not in AGS or MCF7 cells. Demethylation with 5-Aza-2-deoxycytidine upregulated the expression of both these genes in Hep-G2 cells. The expression of DNMT3B, PRMT5, and H4R3me2s increased in E2-treated cells. Chromatin immunoprecipitation showed that E2 treatment recruited PRMT5 and H4R3me2s on FTH1 but not on TFRC. Knockdown of PRMT5, DNMT3B, and Estrogen-receptor alpha rescued FTH1 from E2-induced silencing. However, knockdown of DNMT3B alone blocked the inhibitory effects of E2 on TFRC. Analysis of human liver tissues in publicly available datasets showed that FTH1 and TFRC are highly expressed in primary liver tumours, but a lower expression is associated with better survival. Interestingly, we showed that the silencing of FTH1 and/or TFRC inhibited carcinogenesis in Hep-G2 cells. For the first time, our findings uncovered the novel signalling pathway involved in the protective effects of E2 against liver cancer. Graphical Abstract
SAK3 Administration Improves Spine Abnormalities and Cognitive Deficits in AppNL-G-F/NL-G-F Knock-in Mice by Increasing Proteasome Activity through CaMKII/Rpt6 Signaling

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by neuropathological hallmarks consisting of accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFT). Recently, we have identified a new AD therapeutic candidate, ethyl-8′-methyl-2′,4-dioxo-2-(piperidin-1-yl)-2′H-spiro[cyclopentane-1,3′-imidazo [1,2-a] pyridin]-2-ene-3-carboxylate (SAK3), which ameliorates the AD-like pathology in AppNL-F/NL-F knock-in mice. However, the detailed mechanism underlying the therapeutic effects of SAK3 remains unclear. In this study, we found that SAK3 administration improved the reduced proteasome activity through the activation of CaMKII/Rpt6 signaling in AppNL-F/NL-F knock-in (NL-G-F) mice. Moreover, spine abnormalities observed in NL-G-F mice were significantly reversed by SAK3 administration. Along with this, cognitive impairments found in NL-G-F mice were markedly ameliorated by SAK3. In summary, our data suggest that SAK3 administration increases the activity of the proteasome via activation of the CaMKII/Rpt6 signaling pathway, contributing to improvements in spine abnormalities and cognitive deficits in NL-G-F mice. Overall, our findings suggest that SAK3 might be a new attractive drug candidate, representing a new mechanism for the treatment of AD pathology.
Neurologic manifestations in hospitalized patients with COVID-19

Objective The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurologic symptoms have been reported as part of the clinical spectrum of the disease. We aimed to determine whether neurologic manifestations are common in hospitalized patients with COVID-19 and to describe their main characteristics. Methods We systematically reviewed all patients diagnosed with COVID-19 admitted to the hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurologic clinical manifestations, and complementary tests were analyzed. Results Of 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men), 57.4% developed some form of neurologic symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n = 1), Guillain-Barré syndrome (n = 1), and optic neuritis (n = 1) were also reported, but less frequent. Neurologic complications were the main cause of death in 4.1% of all deceased study participants. Conclusions Neurologic manifestations are common in hospitalized patients with COVID-19. In our series, more than half of patients presented some form of neurologic symptom. Clinicians need to maintain close neurologic surveillance for prompt recognition of these complications. The mechanisms and consequences of severe acute respiratory syndrome coronavirus type 2 neurologic involvement require further studies.
Chest Radiography Features Help to Predict a Favorable Outcome in Patients with Coronavirus Disease 2019

It was with great interest that we read the study by Dr Toussie and colleagues, published in Radiology online on May 14, 2020 (1). In this retrospective study of 338 patients aged 21–50 years with confirmed reverse transcriptase–polymerase chain reaction (RT-PCR) coronavirus disease 2019 (COVID-19) diagnosis, a chest radiography severity score was assigned, dividing the lungs into three zones according to the presence (score of 1) or absence (score of 0) of opacity in each zone. Chest radiography score of 3 or greater proved to be an independent predictor of intubation. In this regard, we would like to present some interesting data from our institution in Milan (Italy) that could cast new light on this topic. We retrospectively assessed the prognostic value of chest radiography performed at initial presentation in a series of patients with diagnosis-confirmed RT-PCR COVID-19 by using the chest radiography severity score proposed by Dr Wong and colleagues (2). This classification depends on the extent of involvement by consolidation or ground-glass opacities (GGOs) (score of 0, no involvement; 1, ,25%; 2, 25%–50%; 3, 50%–75%; 4, 75% involvement), with a maximum score of 8. Two experienced cardiothoracic radiologists (M.C., with 10 years of experience, and G.O., with 25 years of experience) assessed the presence of GGO and consolidation (3), and independently assigned the severity score. Demographic data, comorbidities, and symptoms at arrival were collected. The primary outcome of interest for this study was a mild disease course, defined by no need for hospitalization or hospitalization duration less than 4 days, without any form of assisted ventilation. The relationship between the outcome with chest radiography severity score, radiologic features, and demographic and clinical parameters was investigated by fitting a logistic regression model. We enrolled 246 patients (170 male patients; age range, 30–95 years; mean age, 63 years 6 16 [standard deviation]). Interobserver agreement was excellent, with Cohen k coefficient of 0.9. Independent predictors with statistically significant inverse correlation with mild outcome were as follows: age (odds ratio [OR], 0.92; 95% confidence interval [CI]: 0.88, 0.95; P , .001), chest radiography severity score of 3 or greater (OR, 0.24; 95% CI: 0.69, 0.81; P , .001), and presence of GGOs (OR, 3.79; 95% CI: 0.12, 11.98; P , .02). Sex was correlated with the outcome, with favorable outcome in female patients (OR, 0.05; 95% CI: 0.01, 0.22; P , .001). Our results support the role of chest radiography as a first-line triage tool in detecting COVID-19 pneumonia. We congratulate Dr Toussie and colleagues for their article and for striving to optimize treatment of patients with COVID-19.
Effect of a lactate‐guided conditioning program on heart rate variability obtained using 24-Holter electrocardiography in Beagle dogs

The dogs’ responses to training exercise are seldom monitored using physiological variables, and cardiac autonomic regulation (CAR) is a relevant determinant of endurance-training adaptation. There are studies in the literature establishing that regular exercise could interfere with CAR in dogs, measured by heart rate and vagal-derived indexes of heart-rate-variability (HRV). However, few studies were found using a prescribed training program based on the lactate threshold (LT) to determine HRV by a 24-h Holter analysis. The purpose of this study was to test whether an endurance-training program (ETP) guided individually by LT raises time-domain measures of HRV in healthy Beagle dogs. Twenty dogs were assigned to two groups: control (C) and trained (T). The dogs from group T underwent an incremental exercise test (IET) to determine their LT. Both LT and velocity corresponding to the LT (VLT) was determined by visual inspection. T group performed an eight-week endurance-training program consisting of treadmill runs set to 70–80% of the VLT. Next, dogs from the group T have submitted to IET again. The maximal velocities (Vmax) at which achieved by the trained dogs in both IETs were determined. The group S did not undergo IETs or ETP. HRV was determined by the 24-hour-Holter at rest, before and on the 2°, 4°, 6° and 8° training weeks. To examine the HR impact on HRV, standard HRV variables were normalized to prevailing HR. VLT and Vmax rose in group T, indicating an improvement of dogs’ aerobic and anaerobic capacity. The normalized standard HRV indexes were relatively attenuated since these variables had a reduction in the degree of correlation concerning an average HR. The ETP resulted in decreased resting heart rate and increased time-domain indices, highlighting the log-transformed square root of the mean sum of the squared differences between R–R intervals (Ln rMSSD). The lactate-guided endurance-training program could lead to better parasympathetic cardiac modulation in Beagle dogs.
Serum PD-1/PD-L1 Levels, Tumor Expression and PD-L1 Somatic Mutations in HER2-Positive and Triple Negative Normal-Like Feline Mammary Carcinoma Subtypes

Tumor microenvironment has gained great relevance due to its ability to regulate distinct checkpoints mediators, orchestrating tumor progression. Serum programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) levels were compared with healthy controls and with serum cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and tumor necrosis factor-alpha (TNF-α) levels in order to understand the role of PD-1/PD-L1 axis in cats with mammary carcinoma. PD-1 and PD-L1 expression was evaluated in tumor-infiltrating lymphocytes (TILs) and cancer cells, as the presence of somatic mutations. Results showed that serum PD-1 and PD-L1 levels were significantly higher in cats with HER2-positive (p = 0.017; p = 0.032) and triple negative (TN) normal-like mammary carcinomas (p = 0.004; p = 0.015), showing a strong positive correlation between serum CTLA-4 and TNF-α levels. In tumors, PD-L1 expression in cancer cells was significantly higher in HER2-positive samples than in TN normal-like tumors (p = 0.010), as the percentage of PD-L1-positive TILs (p = 0.037). PD-L1 gene sequencing identified two heterozygous mutations in exon 4 (A245T; V252M) and one in exon 5 (T267S). In summary, results support the use of spontaneous feline mammary carcinoma as a model for human breast cancer and suggest that the development of monoclonal antibodies may be a therapeutic strategy.
STRUCTURE, LIFE HISTORY AND SYSTEMATICS OF RHOICOSPHENIA (BACILLARIOPHYTA). II. AUXOSPORE FORMATION AND PERIZONIUM STRUCTURE OF RH. CURVATA 1

Reproduction in Rhoicosphenia curvata (Kütz.) Grun. is isogamous. The two auxospores formed expand parallel to the apical axes of the gametangial cells. Expansion is bipolar and leads to the formation of a slightly curved, tapering cell, in which the initial valves are laid down. The perizonium consists of transverse and longitudinal bands. The transverse series, of 35 or so bands, is laid down centrifugally as the auxospore expands and can be classified into three groups on the basis of band morphology. All except the central band are open hoops, orientated so that their ends lie in the midline of the less convex, ventral side of the auxospore. The bands have fimbriate margins on one or both sides, and overlap one another from center to either pole. The longitudinal series includes 5 bands—a wide central band, with two on either side: again, the bands overlap one another from the center outwards. The initial epivalve of the new generation forms beneath the dorsal side of the auxospore, on the opposite side from the longitudinal perizonial series. Comparisons are made with other genera and the relevance of auxospore studies to an understanding of diatom morphogenesis is discussed.
Assessing the surgical outcome of the "chopsticks" technique in endoscopic transsphenoidal adenoma surgery.

OBJECTIVE The "chopsticks" technique is a 3-instrument, 2-hand mononostril technique that has been recently introduced in endoscopic neurosurgery. It allows a dynamic surgical view controlled by one surgeon only while keeping bimanual dissection. Being a mononostril approach, it requires manipulation of the mucosa of one nasal cavity only. The rationale of the technique is to reduce nasal morbidity without compromising surgical results and complication rates. There are, however, no data available on its results in endoscopic surgery (transsphenoidal surgery [TSS]) for pituitary adenoma. METHODS The authors performed a cohort analysis of prospectively collected data on 144 patients (156 operations) undergoing TSS using the chopsticks technique with 3T intraoperative MRI. All patients had at least 3 months of postoperative neurosurgical, endocrinological, and rhinological follow-up (Sino-Nasal Outcome Test-20 [SNOT-20] and Sniffin' Sticks). The surgical technique is described, and the achieved gross-total resection (GTR) and extent of resection (EOR) together with patients' clinical outcomes and complications are descriptively reported. RESULTS On 3-month postoperative MRI, GTR was achieved in 71.2% of patients with a mean EOR of 96.7%. GTR was the surgical goal in 122 of 156 cases and was achieved in 106 of 122 (86.9%), with a mean EOR of 98.7% (median 100%, range 49%-100%). There was no surgical mortality. At a median follow-up of 15 months (range 3-70 months), there was 1 permanent neurological deficit. As of the last available follow-up, 11.5% of patients had a new pituitary single-axis deficit, whereas 26.3% had improvement in endocrinological function. Three patients had new postoperative hyposmia. One patient had severe impairment of sinonasal function (SNOT-20 score > 40). The operation resulted in endocrine remission in 81.1% of patients with secreting adenomas. CONCLUSIONS This study shows that the chopsticks technique confers resection and morbidity results that compare favorably with literature reports of TSS. This technique permits a single surgeon to perform effective endoscopic bimanual dissection through a single nostril, reducing manipulation of healthy tissue and thereby possibly minimizing surgical morbidity.