Many exciting advances in cancer-related telomere biology have been made in the past decade. Of these recent advances, great progress has also been made with respect to the Alternative Lengthening of Telomeres (ALT) pathway. Along with a better understanding of the molecular mechanism of this unique telomere maintenance pathway, many studies have also evaluated ALT activity in various cancer subtypes. We first briefly review and assess a variety of commonly used ALT biomarkers. Then, we provide both an update on ALT-positive (ALT+) tumor prevalence as well as a systematic clinical assessment of the presently studied ALT+ malignancies. Additionally, we discuss the pathogenetic alterations in ALT+ cancers, for example, the mutation status of ATRX and DAXX, and their correlations with the activation of the ALT pathway. Finally, we highlight important ALT+ clinical associations within each cancer subtype and subdivisions within, as well as their prognoses. We hope this alternative perspective will allow scientists, clinicians, and drug developers to have greater insight into the ALT cancers so that together, we may develop more efficacious treatments and improved management strategies to meet the urgent needs of cancer patients.

No vertebrate, living or extinct, is known to have possessed an odd number of limbs. Despite this ‘forbidden phenotype’, gaits that use odd numbers of limbs (e.g. tripedalism or pentapedalism) have evolved in both avian and mammalian lineages. Tripedal locomotion is commonly employed by parrots during climbing, who use their beaks as an additional support. However, it is unclear whether the beak functions simply as a stabilizing hook, or as a propulsive limb. Here, we present data on kinetics of tripedal climbing in six rosy-faced lovebirds (Agapornis roseicollis). Our findings demonstrate that parrots use cyclical tripedal gaits when climbing and the beak and hindlimbs generate comparable propulsive and tangential substrate reaction forces and power. Propulsive and tangential forces generated by the beak are of magnitudes equal to or greater than those forces generated by the forelimbs of humans and non-human primates during vertical climbing. We conclude that the feeding apparatus and neck flexors of parrots have been co-opted to function biomechanically as a propulsive third limb during vertical climbing. We hypothesize that this exaptation required substantive alterations to the neuromuscular system including enhanced force-generating capabilities of the neck flexors and modifications to locomotor central pattern generators.

Breast Cancer 1 (BRCA1) gene is a well-characterized tumor suppressor gene, mutations of which are primarily found in women with breast and ovarian cancers. BRCA1-associated RING domain 1 (BARD1) gene has also been identified as an important tumor suppressor gene in breast, ovarian, and uterine cancers. Underscoring the functional significance of the BRCA1 and BARD1 interactions, prevalent mutations in the BRCA1 gene are found in its RING domain, through which it binds the RING domain of BARD1. BARD1-BRCA1 heterodimer plays a crucial role in a variety of DNA damage response (DDR) pathways, including DNA damage checkpoint and homologous recombination (HR). However, many mutations in both BARD1 and BRCA1 also exist in other domains that significantly affect their biological functions. Intriguingly, recent genome-wide studies have identified various single nucleotide polymorphisms (SNPs), genetic alterations, and epigenetic modifications in or near the BARD1 gene that manifested profound effects on tumorigenesis in a variety of non-breast and non-gynecological cancers. In this review, we will briefly discuss the molecular functions of BARD1, including its BRCA1-dependent as well as BRCA1-independent functions. We will then focus on evaluating the common BARD1 related SNPs as well as genetic and epigenetic changes that occur in the non-BRCA1-dominant cancers, including neuroblastoma, lung, and gastrointestinal cancers. Furthermore, the pro- and anti-tumorigenic functions of different SNPs and BARD1 variants will also be discussed.

Positional behaviors have been broadly quantified across the Order Primates, and in several other mammalian lineages, to contextualize adaptations to, and evolution within, an arboreal environment. Outside of Mammalia, however, such data are yet to be reported. In this study, we present the first quantitative report of positional behavior within Aves, presenting 11,246 observations of scan sampling data from a colony of Monk Parakeets (Myiopsitta monachus) from Brooklyn, New York City. Each scan recorded locomotor and postural behavior and information about weather condition, temperature, and substrate properties (e.g., type, size, orientation). A distinction was also recorded between natural and artificial substrates. Parrots exhibited a strong preference for small and terminal branches, a selection which may reflect targeted foraging of new fruit growth and leaf-buds. We further observed that the gait transition from walking to sidling appears primarily driven by substrate size, with the former preferred on the ground and on large, broad substrates and the latter used to navigate smaller branches. Finally, we observed an increase in locomotor diversity on artificial versus naturally occurring substrates. This demonstrates the importance of a flexible behavioral repertoire in facilitating a successful transition towards an urban landscape in introduced species.

Prokinesis, a mode of avian cranial kinesis involving motion between the neurocranium and upper beak, has long been investigated in biomechanical analyses of avian feeding and drinking. However, the modern avian beak is also used for non-feeding functions. Here, we investigate the dual function of prokinesis in the feeding and locomotor systems of the rosy-faced lovebird (Agapornis roseicollis). Lovebirds and other parrots utilize their beak both during feeding and as a third limb during vertical climbing. Thus, we experimentally measured both force-generating potential and movement of the rosy-faced lovebird mandible and maxilla (via prokinetic flexion of the craniofacial hinge) during tripedal climbing and mandibular/maxillary adduction. We found that whereas the maxilla is primarily responsible for generating force during locomotion, the mandible is primarily responsible for generating force during forceful jaw adduction, hinting at a remarkable capacity to alter prokinetic function with differing neuromuscular control. The ability of the prokinetic apparatus to perform functions with competing optimality criteria via modulation of motor control illustrates the functional plasticity of the avian cranial kinesis and sheds new light on the adaptive significance of cranial mobility.