Cranial osteology of Hypoptophis (Aparallactinae : Atractaspididae: Caenophidia), with a discussion on the evolution of its fossorial adaptations

Fossoriality evolved early in snakes, and has left its signature on the cranial morphology of many extinct Mesozoic and early Caenozoic forms. Knowledge of the cranial osteology of extant snakes is indispensable for associating the crania of extinct lineages with a particular mode of life; this applies to fossorial taxa as well. In the present work, we provide a detailed description of the cranium of Hypoptophis wilsonii, a member of the subfamily Aparallactinae, using micro-computed tomography (CT). This is also the first thorough micro-CT-based description of any snake assigned to this African subfamily of predominantly mildly venomous, fossorial, and elusive snakes. The cranium of Hypoptophis is adapted for a fossorial lifestyle, with increased consolidation of skull bones. Aparallactines show a tendency toward reduction of maxillary length by bringing the rear fangs forward. This development attains its pinnacle in the sister subfamily Atractaspidinae, in which the rear fang has become the "front fang" by a loss of the part of the maxilla lying ahead of the fang. These dentitional changes likely reflect adaptation to subdue prey in snug burrows. An endocast of the inner ear of Hypoptophis shows that this genus has the inner ear typical of fossorial snakes, with a large, globular sacculus. A phylogenetic analysis based on morphology recovers Hypoptophis as a sister taxon to Aparallactus. We also discuss the implications of our observations on the burrowing origin hypothesis of snakes.Peer reviewe

Pricing best sellers and traffic generators: the role of asymmetric cross-selling

Among the many items online retailers sell, some stand out as best sellers and are often sold at considerable discounts. Best seller discounting can encourage customer traffic and the purchase of a basket of other products in the same transaction. Although most studies treat retailers as symmetric, the cross-selling potential is generally asymmetric across retailers, since some online retailers have more products to sell. In addition, the cross-selling effect works both ways – customers intending to buy a best seller may buy other items in their shopping basket, while other customers intending to buy a basket may buy a best seller while visiting the retailer. The authors model the pricing implications of this rich variety of asymmetric cross-selling, with both best sellers and typical baskets acting as traffic generators and cross-sold products. The common wisdom that loss leader pricing leads to neither a significant increase in store traffic nor an increase in profits does not apply in an asymmetric case where one retailer has more products to cross-sell. The cross-selling potential of products even far down the best seller list is demonstrated. Empirical analyses provide support for key findings of the theoretical model using book pricing and sales rank data from multiple online retailers

Ultraconserved elements-based phylogenomic systematics of the snake superfamily Elapoidea, with the description of a new Afro-Asian family

The highly diverse snake superfamily Elapoidea is considered to be a classic example of ancient, rapid radiation. Such radiations are challenging to fully resolve phylogenetically, with the highly diverse Elapoidea a case in point. Previous attempts at inferring a phylogeny of elapoids produced highly incongruent estimates of their evolutionary relationships, often with very low statistical support. We sought to resolve this situation by sequencing over 4,500 ultraconserved element loci from multiple representatives of every elapoid family/sub-family level taxon and inferring their phylogenetic relationships with multiple methods. Concatenation and multispecies coalescent based species trees yielded largely congruent and well-supported topologies. Hypotheses of a hard polytomy were not retained for any deep branches. Our phylogenies recovered Cyclocoridae and Elapidae as diverging early within Elapoidea. The Afro-Malagasy radiation of elapoid snakes, classified as multiple subfamilies of an inclusive Lamprophiidae by some earlier authors, was found to be monophyletic in all analyses. The genus Micrelaps was consistently recovered as sister to Lamprophiidae. We establish a new family, Micrelapidae fam. nov., for Micrelaps and assign Brachyophis to this family based on cranial osteological syn-apomorphy. We estimate that Elapoidea originated in the early Eocene and rapidly diversified into all the major lineages during this epoch. Ecological opportunities presented by the post-Cretaceous-Paleogene mass extinction event may have promoted the explosive radiation of elapoid snakes.Peer reviewe

Inter-annual variation in movements and passage of seaward migrating European eels at a shrouded Archimedean screw pumping station

The construction of less damaging (here called fish-friendly) pumping stations has taken place in recent years, but it is unknown if they provide efficient and timely passage to migratory fish, such as European eel (Anguilla anguilla (L.)). The pump is often the only downstream passage route and operation, i.e., fish passage opportunity, is temporally variable depending on precipitation and prevailing river levels. Once the pumps are operating, eels must also consider the pumping station an attractive downstream passage route. Here, the movement of seaward migrating silver European eel (n = 59) upstream of a fish-friendly shrouded Archimedean Screw Pump (ASP) was assessed during three migrations (December–March in 2018/19, 2019/20 and 2020/21) with highly contrasting hydrology using acoustic telemetry. The overall passage rate was low (36.8 %) and minimum passage time was 65.2 days during a year with very little pump operation (2018/19), with seven eels tagged with long-life transmitters passing the pumping station the following year (2019/20). Furthermore, the median number of approaches to the pumping station was seven, with 36.8 % (n = 7) approaching more than 10 times. By contrast, passage rate was high (95.0 %), maximum passage time was 2.7 and 34.0 days (minimum = 3 min in both years) and all but one eel passed during the first approach during the two wettest years (2019/20 and 2020/21). Eels were almost exclusively nocturnal, regardless of pump operation, with 96.1 % of total approaches occurring between sunset and sunrise and no eels passed downstream during the day. Ultimately, limited eel passage opportunity during dry periods and a reluctance to pass when operational curtailed the effectiveness of these pumps to provide efficient and timely passage. Thus, measures are required to align pump operation with the timing of eel migration, especially in dry years, and reasons for retreat from the pumping station during operation must be identified and alleviated

The clinical significance of incidental intra-abdominal findings on positron emission tomography performed to investigate pulmonary nodules

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a common cause of cancer-related death. Staging typically includes positron emission tomography (PET) scanning, in which¹⁸F-fluoro-2-dexoy-D-glucose (FDG) is taken up by cells proportional to metabolic activity, thus aiding in differentiating benign and malignant pulmonary nodules. Uptake of FDG can also occur in the abdomen. The clinical significance of incidental intraabdominal FDG uptake in the setting of pulmonary nodules is not well established. Our objective was to report on the clinical significance of incidental intra-abdominal FDG activity in the setting of lung cancer.</p> <p>Methods</p> <p>Fifteen hundred FDG-PET reports for studies performed for lung cancer were retrospectively reviewed for the presence of incidental FDG-positive intraabdominal findings. Patient charts with positive findings were then reviewed and information extracted.</p> <p>Results</p> <p>Twenty-five patients (25/1500) demonstrated incidental intraabdominal FDG uptake thought to be significant (1.7%) with a mean patient age of 71 years. Colonic uptake was most common (n = 17) with 9 (52%) being investigated further. Of these 9 cases, a diagnosis of malignancy was made in 3 patients, pre-malignant adenomas in 2 patients, a benign lipoma in 1 patient and no abnormal findings in the remaining patients. 8 patients were not investigated further (3 diagnosed with metastatic lung cancer and 2 were of advanced age) secondary to poor prognosis.</p> <p>Conclusion</p> <p>Incidental abdominal findings in the colon on FDG-PET scan for work-up of pulmonary nodules need to be further investigated by colonoscopy.</p

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription

Bimodal crystallization at polymer-fullerene interfaces

The growth-kinetics of [6,6]-phenyl C61-butyric acid methyl ester (PCBM) crystals, on two different length-scales, is shown to be controlled by the thickness of the polymer layer within a PCBM-polymer bilayer. Using a model amorphous polymer we present evidence, from in situ optical microscopy and grazing-incidence X-ray diffraction (GIXD), that an increased growth-rate of nanoscale crystals impedes the growth of micron-sized, needle-like PCBM crystals. A combination of neutron reflectivity and GIXD measurements, also allows us to observe the establishment of a liquid-liquid equilibrium composition-profile between the PCBM layer and a polymer-rich layer, before crystallization occurs. While the interfacial composition-profile is independent of polymer-film-thickness, the growth-rate of nanoscale PCBM crystals is significantly larger for thinner polymer films. A similar thickness-dependent behavior is observed for different molecular weights of entangled polymer. We suggest that the behavior may be related to enhanced local-polymer-chain-mobility in nanocomposite thin-films

N348I in the Connection Domain of HIV-1 Reverse Transcriptase Confers Zidovudine and Nevirapine Resistance

Analyzing HIV sequences from a Canadian cohort, Gilda Tachedjian and colleagues identify a common mutation in a little-studied domain of reverse transcriptase that confers resistance to two drug classes

Efficacy and safety of fluticasone/formoterol combination therapy in patients with moderate-to-severe asthma

Background: The inhaled corticosteroid, fluticasone propionate, and the long-acting b2-adrenergic agonist, formoterol fumarate, are both highly effective treatments for bronchial asthma. This study (NCT00393952/EudraCT number: 2006-005989-39) compared the efficacy and safety of fluticasone/formoterol combination therapy (flutiform®; 250/10 mg) administered twice daily (b.i.d.) via a single aerosol inhaler, with the individual components (fluticasone 250 mg b.i.d.; formoterol 10 mg b.i.d.), in adult and adolescent patients with moderate-to-severe asthma. Methods: This was a 12-week, double-blind, randomised, parallel-group, multicentre, placebocontrolled phase 3 study. The co-primary efficacy endpoints were: i) the mean change in the forced expiratory volume in the first second (FEV1) from morning pre-dose at baseline to pre-dose at week 12 (fluticasone/formoterol 250/10 mg vs. formoterol), ii) the mean change in FEV1 from morning pre-dose at baseline to 2 h post-dose at week 12 (fluticasone/formoterol 250/10 mg vs. fluticasone), and iii) the number of patients who discontinued prematurely due to lack of treatment efficacy (fluticasone/formoterol 250/10 mg vs. placebo). The secondary endpoints included measures of lung function, disease control, and asthma symptoms. Safety was assessed based on adverse events, vital signs, and clinical laboratory evaluations. Results: Overall, 395 (70.9%) patients completed the study. Fluticasone/formoterol 250/10 mg b.i.d. was superior to the individual components and placebo for all three co-primary endpoints and demonstrated numerically greater improvements for multiple secondary efficacy analyses. Fluticasone/formoterol combination therapy had a good safety profile over the 12 weeks. Conclusion: Fluticasone/formoterol combination therapy will provide clinicians with an efficacious alternative treatment option for patients with moderate-to-severe asthma

Measurement of the Splitting Function in &ITpp &ITand Pb-Pb Collisions at root&ITsNN&IT=5.02 TeV

Data from heavy ion collisions suggest that the evolution of a parton shower is modified by interactions with the color charges in the dense partonic medium created in these collisions, but it is not known where in the shower evolution the modifications occur. The momentum ratio of the two leading partons, resolved as subjets, provides information about the parton shower evolution. This substructure observable, known as the splitting function, reflects the process of a parton splitting into two other partons and has been measured for jets with transverse momentum between 140 and 500 GeV, in pp and PbPb collisions at a center-of-mass energy of 5.02 TeV per nucleon pair. In central PbPb collisions, the splitting function indicates a more unbalanced momentum ratio, compared to peripheral PbPb and pp collisions.. The measurements are compared to various predictions from event generators and analytical calculations.Peer reviewe