Searching by Rules: Pigeons’ (\u3ci\u3eColumba livia\u3c/i\u3e) Landmark-Based Search According to Constant Bearing or Constant Distance

Pigeons (Columba livia) searched for a goal location defined by a constant relative spatial relationship to 2 landmarks. For one group, landmark-to-goal bearings remained constant while distance varied. For another group, landmark-to-goal distances remained constant while direction varied. Birds were trained with 4 interlandmark distances and then tested with 5 novel interlandmark distances. Overall error magnitude was similar across groups and was larger than previously reported for Clark’s nutcrackers (Nucifraga columbiana). During training, error magnitude increased with interlandmark distance for constant-bearing but not constant-distance birds. Both groups searched less accurately along the axis parallel to landmarks than along the perpendicular axis. Error magnitude increased with novel extrapolated interlandmark distances but not with novel interpolated distances. Results suggest modest geometric rule learning by pigeons

Immune Response to Newcastle Disease Virus Vaccination in a Wild Passerine

We studied the immune response of wild House Sparrows (Passer domesticus) experimentally challenged with different doses of inactivated Newcastle disease virus (NDV) vaccine. We evaluated within-individual cell-mediated and humoral responses in birds kept in outdoor aviaries, over a 6-wk period. Nonbreeding adult House Sparrows developed a significant humoral response to NDV experimental vaccination within 1 wk postchallenge, as measured by hemagglutination inhibition assay; values increased until week 4 and persisted until week 6. Differences among treatments appeared by week 1, with individuals challenged with the highest dose (0.2 mL) eliciting a higher humoral response than the rest (n = 18). By week 4, all individuals vaccinated displayed an increased humoral response, with individuals challenged with the highest dose remaining significantly above responses of individuals vaccinated with the middle dose (0.1 mL, n = 14), but not the lowest dose (0.05 mL, n = 15). The middle and lowest dose responded similarly and significantly different from controls (n = 23). Differences persisted through week 6 postchallenge. Cell-mediated responses were independent of the experimental treatment. All individuals experienced a rise in granulocyte concentration, whereas lymphocyte and monocyte concentrations decreased, most likely as a result of captivity. Adult wild House Sparrows immunochallenged with inactivated NDV vaccine developed a specific humoral response, highlighting the utility of this technique in immunologic and evolutionary ecology studies in wild birds.Peer reviewe

Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of Terminal Oligopyrimidine (TOP) mRNAs on polysomes

The synthesis of adequate amounts of ribosomes is an essential task for the cell. It is therefore not surprising that regulatory circuits exist to organize the synthesis of ribosomal components. It has been shown that defect in ribosome biogenesis (ribosomal stress) induces apoptosis or cell cycle arrest through activation of the tumor suppressor p53. This mechanism is thought to be implicated in the pathophysiology of a group of genetic diseases such as Diamond Blackfan Anemia which are called ribosomopathies. We have identified an additional response to ribosomal stress that includes the activation of eukaryotic translation elongation factor 2 kinase with a consequent inhibition of translation elongation. This leads to a translational reprogramming in the cell that involves the structurally defined group of messengers called terminal oligopyrimidine (TOP) mRNAs which encode ribosomal proteins and translation factors. In fact, while general protein synthesis is decreased by the impairment of elongation, TOP mRNAs are recruited on polysomes causing a relative increase in the synthesis of TOP mRNA-encoded proteins compared to other proteins. Therefore, in response to ribosomal stress, there is a change in the translation pattern of the cell which may help restore a sufficient level of ribosomes

Reactive astrocytes potentiate tumor aggressiveness in a murine glioma resection and recurrence model

Surgical resection is a universal component of glioma therapy. Little is known about the postoperative microenvironment due to limited preclinical models. Thus, we sought to develop a glioma resection and recurrence model in syngeneic immune-competent mice to understand how surgical resection influences tumor biology and the local microenvironment

Introductory biology undergraduate students\u27 mixed ideas about genetic information flow

The core concept of genetic information flow was identified in recent calls to improve undergraduate biology education. Previous work shows that students have difficulty differentiating between the three processes of the Central Dogma (CD; replication, transcription, and translation). We built upon this work by developing and applying an analytic coding rubric to 1050 student written responses to a three‐question item about the CD. Each response was previously coded only for correctness using a holistic rubric. Our rubric captures subtleties of student conceptual understanding of each process that previous work has not yet captured at a large scale. Regardless of holistic correctness scores, student responses included five or six distinct ideas. By analyzing common co‐occurring rubric categories in student responses, we found a common pair representing two normative ideas about the molecules produced by each CD process. By applying analytic coding to student responses preinstruction and postinstruction, we found student thinking about the processes involved was most prone to change. The combined strengths of analytic and holistic rubrics allow us to reveal mixed ideas about the CD processes and provide a detailed picture of which conceptual ideas students draw upon when explaining each CD process

Evolutionarily distinct bacteriophage endolysins featuring conserved peptidoglycan cleavage sites protect mice from MRSA infection

Objectives In the light of increasing drug resistance in Staphylococcus aureus, bacteriophage endolysins [peptidoglycan hydrolases (PGHs)] have been suggested as promising antimicrobial agents. The aim of this study was to determine the antimicrobial activity of nine enzymes representing unique homology groups within a diverse class of staphylococcal PGHs. Methods PGHs were recombinantly expressed, purified and tested for staphylolytic activity in multiple in vitro assays (zymogram, turbidity reduction assay and plate lysis) and against a comprehensive set of strains (S. aureus and CoNS). PGH cut sites in the staphylococcal peptidoglycan were determined by biochemical assays (Park-Johnson and Ghuysen procedures) and MS analysis. The enzymes were tested for their ability to eradicate static S. aureus biofilms and compared for their efficacy against systemic MRSA infection in a mouse model. Results Despite similar modular architectures and unexpectedly conserved cleavage sites in the peptidoglycan (conferred by evolutionarily divergent catalytic domains), the enzymes displayed varying degrees of in vitro lytic activity against numerous staphylococcal strains, including cell surface mutants and drug-resistant strains, and proved effective against static biofilms. In a mouse model of systemic MRSA infection, six PGHs provided 100% protection from death, with animals being free of clinical signs at the end of the experiment. Conclusions Our results corroborate the high potential of PGHs for treatment of S. aureus infections and reveal unique antimicrobial and biochemical properties of the different enzymes, suggesting a high diversity of potential applications despite highly conserved peptidoglycan target site

“You felt like a prisoner in your own self, trapped”: The experiences of Aboriginal people with acquired communication disorders

Purpose: Aboriginal Australians are under-represented in brain injury rehabilitation services despite a high incidence of both stroke and traumatic brain injury in this population. This study aimed to explore the experiences of Aboriginal Australian adults with acquired communication disorders (ACDs) after brain injury for the first time to inform the development of accessible and culturally secure service delivery models. Methods and materials: Semi-structured interviews were undertaken with 32 Aboriginal people who had experienced a brain injury resulting in ACDs (aged 35–79 years) and 18 family members/carers across Western Australia. Thematic analysis identified common themes across participants. Results: Overall themes related to communication (both related to the communication disorder and general healthcare interactions), health and social contexts, recovery, and support, being away from family and country, knowledge and beliefs about brain injury, and follow-up. Conclusions: An increase in healthcare staff’s appreciation of the health and social contexts of Aboriginal people after brain injury is needed in order to improve communication with Aboriginal patients and the ability to offer accessible rehabilitation services. Ongoing support is required, with cultural identity noted as key to ensuring cultural security and ultimately recovery. Involvement of family and other Aboriginal people in recovery processes, as well as access to relevant Aboriginal languages and proximity to ancestral lands is central. Implications for rehabilitation Acknowledgment of cultural identity and strengths through involvement of extended family and Aboriginal Hospital Liaison Officers, access to language and proximity to country all central to rehabilitation planning for Aboriginal people after brain injury. Cultural security training for rehabilitation staff is recommended focusing on clear two-way communication skills to make medical information accessible for Aboriginal patients and to listen to patients’ concerns in a way that respects cultural context. Information regarding practical support and implications for ongoing management of life after brain injury (for the person and their family) is essential, and should supplement the medical-related information provided. Follow-up post discharge from hospital best facilitated through establishing contact with local Aboriginal community through Aboriginal community controlled health services, community elders, and Aboriginal health workers across organisations

Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma

Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced apoptosis in co-cultured human glioblastoma cells. Time-lapse imaging shows that iNSCs are tumouritropic, homing rapidly to co-cultured glioblastoma cells and migrating extensively to distant tumour foci in the murine brain. Multimodality imaging reveals that iNSC delivery of the anticancer molecule TRAIL decreases the growth of established solid and diffuse patient-derived orthotopic glioblastoma xenografts 230- and 20-fold, respectively, while significantly prolonging the median mouse survival. These findings establish a strategy for creating autologous cell-based therapies to treat patients with aggressive forms of brain cancer

Automated analysis of atrial late gadolinium enhancement imaging that correlates with endocardial voltage and clinical outcomes: A 2-center study

This work was supported by the British Heart Foundation PG/10/37/28347, RG/10/11/28457, NIHR Biomedical Research Centre funding, and the ElectroCardioMaths Programme of the Imperial BHF Centre of Research Excellence