Mutual Recognition: The Struggle for Power and Domination

This paper examines Hegel\u27s description of mutual recognition in his Phenomenology of Spirit. On this account, development of a self-consciousness occurs only alongside another, separate and distinct self-consciousness. We find our identity and genuine sense of selfhood through family ties, civil society, and the state. Apart from others, we cease to exist—self-consciousness cannot be found in isolation. With this said, many internal and external complications ensue from obtaining recognition, our greatest desire, from another self which also seeks recognition. Hegel’s Master-Slave dialectic is delineated along with the attainment of self-consciousness through social and political spheres. The emphasis he places on intersubjective relations of recognition for selfhood is compelling; however, his account is too cognitive and political and thus fails to adequately resolve the inequitable power dynamic at hand. Emotionality and friendship both transcend and dismantle the struggle for recognition and should therefore receive more attention in Hegel’s account of attaining recognition

A bone of contention: A dynamic ultrasound assessment of the role of the radial head in the arthrokinematics of the proximal radioulnar joint

INTRODUCTION: The arthrokinematics of the proximal radioulnar joint (PRUJ) are believed to follow the convex-concave rule, meaning that when the convex radial head articulates with the concave radial notch on the ulna, rolling and gliding occur in opposite directions during forearm pronation and supination. Previous research using helical computerized tomography (CT) identified that the sequence of joint actions is in contrast with this rule, which would indicate a posterior glide of the radius on the ulna during pronation movement and the converse during supination. OBJECTIVES: The aims of this study are to determine the arthrokinematics of the PRUJ while being assessed via ultrasound (US) imaging and to assess the impact the direction of joint mobilization has on active and passive range of motion (ROM) during forearm supination and pronation at the PRUJ. METHODS: A convenience sample of 53 healthy individuals were recruited. The arthrokinematics of the PRUJ were observed via US cine-loops. A linear US transducer was applied in the transverse plane and placed over the radial head during all testing conditions. A metronome standardized the rate of forearm pronation and supination at 1Hz (60 bpm) during US cine-loops acquisition. Radial head motion was assessed in two different elbow positions during US and joint range of motion assessment. The elbow was flexed to 90° with a neutral forearm position and fully extended with a neutral forearm position. The glenohumeral joint was stabilized during all testing conditions. A repeated measures design randomizing joint mobilization direction to the radial head was utilized to assess forearm pronation and supination via inclinometer data measured in degrees. Joint glides were applied to the radial head according to the convex-concave rule to facilitate forearm supination and pronation. An anteromedial glide to facilitate forearm supination and a posterolateral glide to facilitate forearm pronation. A metronome standardized the rate of joint mobilization at a rate 2Hz (120 bpm). A bubble inclinometer assessed active and passive PRUJ ROM at the wrist during all testing conditions. RESULTS:US imaging cine-loops showed the radial head rolled anteromedially during pronation and posterolaterally during supination, with no translation/gliding evident. Multivariate analysis revealed that the direction of joint mobilization had a significant impact on ROM F(1,47.0)= 6.964, p=.011, partial η2 =.129), with anterior mobilization increasing pronation and posterior mobilization increasing supination. Supination ROM was significantly increased F1(1, 47.0) = 78.03, p CONCLUSION: Our findings are in conflict with the convex-concave rule, which is frequently used by physical therapists to improve joint motion. Should we now reconsider applying this rule to improve joint ROM at the PRUJ

Psychometric evaluation of a working memory assessment measure in young children with Down syndrome

BackgroundWorking memory involves the temporary storage and manipulation of information and is frequently an area of challenge for individuals with Down syndrome (DS). Despite the potential benefits of intervention, laboratory assessments of working memory that could capture intervention effects have not undergone rigorous evaluation for use with young children with DS. It is critical to evaluate assessments of working memory in young children with DS to ensure the reliable and accurate measurement of performance.AimThis study evaluated an adapted laboratory measure of working memory for young children with DS 2-8 years old.MethodA self-ordered pointing task, the Garage Game, was administered to 78 children with DS (mean = 5.17 years; SD = 1.49). Adaptations were made to the task to minimize potential DS phenotype-related language and motor confounds.ResultsResults indicate that the measure is feasible, scalable, and developmentally sensitive, with minimal floor and practice effects for this population within this chronological and developmental age range.ConclusionThese findings demonstrate that the Garage Game is promising for use in studies of early working memory and treatment trials that aim to support the development of this critical dimension of executive functioning for children with DS

Substance-specific readiness to change among sexual and gender minority men who use crystal methamphetamine

A patient-oriented approach to addressing high levels of polysubstance use among sexual and gender minority men (SGM) who use crystal methamphetamine (CM) requires an understanding of which drugs they would like to change their use of. We examined readiness to change for 24 separate substances. Participants were SGM, aged 18+, living with Canada, who used CM in the past six months that were recruited through advertisements on socio-sexual networking applications. Frequency of use and readiness to change were descriptively analyzed and associations between frequency of use and readiness to change were assessed. Only slightly more than half (53.1%) of CM-using SGM were ready now, soon, or in the future to change substance use. Participants were most ready to change their tobacco, methamphetamine, and barbiturate use. Greater frequency of use was associated with greater readiness to change for all drugs in which daily or almost daily use was common. SGM participants reported high levels of comfort being asked about their substance use from primary care, mental health, and queer-identified health professionals. Interventions addressing multiple and specific substances are needed in health care settings serving SGM who use CM. Screening, brief interventions, and referral to treatment (SBIRT) in these settings may help identify those ready to address their substance use. Harm reduction interventions should offer supports for those not wanting to change their substance use—which includes most SGM for most of the drugs they use

The updated mouse universal genotyping array bioinformatic pipeline improves genetic QC in laboratory mice

The MiniMUGA genotyping array is a popular tool for genetic quality control of laboratory mice and genotyping samples from most experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve the array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA. Here, we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for classical inbred strains and substrains, and increase the number of constructs reliably detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have updated the layout of the report to simplify the interpretation and completeness of the analysis and added a section summarizing the ideogram in table format. These changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.United States. National Institutes of Health (R01GM107536)Alex's Lemonade Stand FoundationHoward Hughes Medical InstituteBoston Children's Hospital. Manton Center for Orphan Disease ResearchNational Institute of General Medical Sciences (U.S.) (T32GM007753

A Survey of New Temperature-Sensitive, Embryonic-Lethal Mutations in C. elegans: 24 Alleles of Thirteen Genes

To study essential maternal gene requirements in the early C. elegans embryo, we have screened for temperature-sensitive, embryonic lethal mutations in an effort to bypass essential zygotic requirements for such genes during larval and adult germline development. With conditional alleles, multiple essential requirements can be examined by shifting at different times from the permissive temperature of 15°C to the restrictive temperature of 26°C. Here we describe 24 conditional mutations that affect 13 different loci and report the identity of the gene mutations responsible for the conditional lethality in 22 of the mutants. All but four are mis-sense mutations, with two mutations affecting splice sites, another creating an in-frame deletion, and one creating a premature stop codon. Almost all of the mis-sense mutations affect residues conserved in orthologs, and thus may be useful for engineering conditional mutations in other organisms. We find that 62% of the mutants display additional phenotypes when shifted to the restrictive temperature as L1 larvae, in addition to causing embryonic lethality after L4 upshifts. Remarkably, we also found that 13 out of the 24 mutations appear to be fast-acting, making them particularly useful for careful dissection of multiple essential requirements. Our findings highlight the value of C. elegans for identifying useful temperature-sensitive mutations in essential genes, and provide new insights into the requirements for some of the affected loci

A Search for Technosignatures Around 11,680 Stars with the Green Bank Telescope at 1.15-1.73 GHz

We conducted a search for narrowband radio signals over four observing sessions in 2020-2023 with the L-band receiver (1.15-1.73 GHz) of the 100 m diameter Green Bank Telescope. We pointed the telescope in the directions of 62 TESS Objects of Interest, capturing radio emissions from a total of ~11,680 stars and planetary systems in the ~9 arcminute beam of the telescope. All detections were either automatically rejected or visually inspected and confirmed to be of anthropogenic nature. In this work, we also quantified the end-to-end efficiency of radio SETI pipelines with a signal injection and recovery analysis. The UCLA SETI pipeline recovers 94.0% of the injected signals over the usable frequency range of the receiver and 98.7% of the injections when regions of dense RFI are excluded. In another pipeline that uses incoherent sums of 51 consecutive spectra, the recovery rate is ~15 times smaller at ~6%. The pipeline efficiency affects calculations of transmitter prevalence and SETI search volume. Accordingly, we developed an improved Drake Figure of Merit and a formalism to place upper limits on transmitter prevalence that take the pipeline efficiency and transmitter duty cycle into account. Based on our observations, we can state at the 95% confidence level that fewer than 6.6% of stars within 100 pc host a transmitter that is detectable in our search (EIRP > 1e13 W). For stars within 20,000 ly, the fraction of stars with detectable transmitters (EIRP > 5e16 W) is at most 3e-4. Finally, we showed that the UCLA SETI pipeline natively detects the signals detected with AI techniques by Ma et al. (2023).Comment: 22 pages, 9 figures, submitted to AJ, revise

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

p53 and TAp63 promote keratinocyte proliferation and differentiation in breeding tubercles of the zebrafish

p63 is a multi-isoform member of the p53 family of transcription factors. There is compelling genetic evidence that ΔNp63 isoforms are needed for keratinocyte proliferation and stemness in the developing vertebrate epidermis. However, the role of TAp63 isoforms is not fully understood, and TAp63 knockout mice display normal epidermal development. Here, we show that zebrafish mutants specifically lacking TAp63 isoforms, or p53, display compromised development of breeding tubercles, epidermal appendages which according to our analyses display more advanced stratification and keratinization than regular epidermis, including continuous desquamation and renewal of superficial cells by derivatives of basal keratinocytes. Defects are further enhanced in TAp63/p53 double mutants, pointing to partially redundant roles of the two related factors. Molecular analyses, treatments with chemical inhibitors and epistasis studies further reveal the existence of a linear TAp63/p53->Notch->caspase 3 pathway required both for enhanced proliferation of keratinocytes at the base of the tubercles and their subsequent differentiation in upper layers. Together, these studies identify the zebrafish breeding tubercles as specific epidermal structures sharing crucial features with the cornified mammalian epidermis. In addition, they unravel essential roles of TAp63 and p53 to promote both keratinocyte proliferation and their terminal differentiation by promoting Notch signalling and caspase 3 activity, ensuring formation and proper homeostasis of this self-renewing stratified epithelium