Iron homeostasis and post-hemorrhagic hydrocephalus: A review

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain development, characterizes our understanding of iron transport in the developing brain, and describes potential mechanisms by which iron overload may cause PHH and brain injury. We also review novel preclinical treatments for IVH that specifically target iron. Understanding iron handling within the brain and central nervous system may provide a basis for preventative, targeted treatments for iron-mediated pathogenesis of GMH-IVH and PHH

Nature

The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different basolateral amygdala (BLA) projections are potentiated following reward or punishment learning1–7. However, we do not yet understand how valence specific information is routed to the BLA neurons with the appropriate downstream projections. Nor do we understand how to reconcile the subsecond timescales of synaptic plasticity8–11 with the longer timescales separating the predictive cues from their outcomes. Here, we demonstrate that neurotensin (NT) neurons in the paraventricular nucleus of the thalamus (PVT) projecting to the BLA (PVT-BLA:NT) mediate valence assignment by exerting concentration-dependent modulation in BLA during associative learning. We found that optogenetic activation of the PVT-BLA:NT projection promotes reward learning, while PVT-BLA projection-specific Nt gene knockout augments punishment learning. Using genetically encoded calcium and NT sensors, we further revealed that both calcium dynamics within the PVT-BLA:NT projection and NT concentrations in the BLA are enhanced after reward learning and reduced after punishment learning. Finally, we showed that CRISPR-mediated knockout of the Nt gene in the PVT-BLA pathway blunts BLA neural dynamics and attenuates the preference to active behavioral strategies to reward and punishment predictive cues. Taken together, we have identified NT as a neuropeptide that signals valence in the BLA, and showed that NT is a critical neuromodulator that orchestrates positive and negative valence assignment in amygdala neurons by extending valence-specific plasticity to behaviorally-relevant timescales

Brain stains: optimization of immunohistochemical methods for cleared thick neural tissue

Populations of GABAergic interneurons in the prefrontal cortex have been implicated in control and coordination of complex behaviors such as motivation and decision-making. Although the functions of each of the main GABAergic subtypes, SST, PV, and VIP, have been extensively investigated independently, a lack of techniques allowing simultaneous recording has precluded the ability to characterize the interactions between these cell types. Staining for markers of GABA cell types in thick tissue, and relating identities back to in vivo recordings, will allow explicit and direct characterization of how activity covaries in these populations. However, there has been minimal success when staining for GABAergic subtypes in thick tissue. I interrogated the different factors that might be affecting successful thick tissue staining using the Cuboid Method which enables controlled and efficient thick tissue preparation, staining, and experimental testing. Fixation, with both paraformaldehyde and glutaraldehyde, was observed to be a major factor influencing the ability of different SST, PV, and VIP antibodies to label their epitopes in thick tissue. Additionally, fixation appeared to affect SST and VIP staining differently than PV staining. SDS treatment prior to staining was shown to be compatible with GABAergic subtype staining while SDS treatment after staining was shown to dramatically decrease staining signal. Like others’ findings, blocking was shown to be unnecessary for better PV and SST staining. Lastly, relative proportions of SST, PV, and VIP in the PFC and their staining patterns in thick tissue matched results from previous work in thin tissue to support that staining was successful and also accurate. This research provides the knowledge necessary to successfully stain for SST, PV, and VIP in thick tissue in addition to showing the efficacy of the Cuboid Method for testing factors affecting staining in thick tissue

“Too Soon” to count? How gender and race cloud notability considerations on Wikipedia

While research has explored the extent of gender bias and the barriers to women's inclusion on English-language Wikipedia, very little research has focused on the problem of racial bias within the encyclopedia. Despite advocacy groups' efforts to incrementally improve representation on Wikipedia, much is unknown regarding how biographies are assessed after creation. Applying a combination of web-scraping, deep learning, natural language processing, and qualitative analysis to pages of academics nominated for deletion on Wikipedia, we demonstrate how Wikipedia's notability guidelines are unequally applied across race and gender. We find that online presence predicts whether a Wikipedia page is kept or deleted for white male academics but that this metric is idiosyncratically applied for female and BIPOC academics. Further, women's pages, regardless of race, were more likely to be deemed “too soon” for Wikipedia. A deeper analysis of the deletion archives reveals that when the tag is used on a woman's biography it is done so outside of the community guidelines, referring to one's career stage rather than media/online coverage. We argue that awareness of hidden biases on Wikipedia is critical to the objective and equitable application of the notability criteria across race and gender both on the encyclopedia and beyond

Spinal calcifying pseudoneoplasms of the neuraxis: A case report and review of the literature

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, non-neoplastic, slow-growing tumors that can present anywhere throughout the central nervous system. While the etiology of these lesions remains unknown, the mainstay of treatment is surgical excision. We describe a case of CAPNON at our institution in a 66 year-old female patient who presented with 5 months of pain and burning sensation in her thigh. On MRI, an intradural extramedullary lesion was identified at the level of T11-T12. The mass was surgically excised and the patient reported resolution of her symptoms by her six week follow-up appointment. We reviewed 79 spinal CAPNON cases, covering all cases reported in the literature thus far. In summary, we find that spinal CAPNON are most commonly lumbar and extradural in location, with pain as the most common presenting symptom. Lesions are well-defined and hypointense on T1 and T2 MRI sequence. The majority of cases had favorable surgical outcomes with near complete resolution of pain and associated symptoms

Complete Hydatidiform Mole with a Coexisting Viable Male Fetus Detected by Cell-Free DNA

Complete hydatidiform mole with coexisting fetus (CHMCF) is rare, and diagnosis is challenging due to limited data. Here, we present the case of a patient with noninvasive prenatal test (NIPT) resulting in “likely molar pregnancy” in the second trimester. Subsequent ultrasound confirmed a cystic appearing portion of the placenta. At 22 weeks, the patient delivered a demised fetus and two placentas. Pathology was consistent with CHMCF. This case is the first to show primary detection of a CHMCF with single-nucleotide polymorphism (SNP)-based NIPT prior to ultrasound identification. Our case suggests the use of SNP-based NIPT as an alternative noninvasive method to guide shared decision-making and clinical management for patients with this diagnosis

Wildlife crime : The problems of enforcement

Environmental and wildlife crime appear recently to be benefitting from an increasing profile amongst those agencies tasked with their control, as well as receiving growing criminological attention. Despite this, those with responsibilities in this area report that it remains marginalised, receiving limited resources and suffering from a lack of political impetus to push such problems higher up the agenda. This is particularly so for those agencies, such as the police, that may be seen to have many more pressing objectives. This discussion paper considers the problems of relying on an enforcement approach to controlling such offences, taking, as an example, those activities that may be termed ‘wildlife crime’, focusing on the situation in England and Wales. Firstly, the legislative framework that criminalises harm or exploitation of wildlife is presented, alongside the main enforcement methods used. Next, the problems facing an enforcement approach are critically considered, the key issues being: under-resourcing and marginalisation, the large ‘dark figure’ of wildlife crime, the possibility of corruption, the lack of seriousness with which such crimes are viewed, and the lack of deterrent effect. Finally, responses to the problems of enforcement are presented, categorised as either methods to improve enforcement or, as the author advocates, methods which are alternatives to enforcement (such as adopting a crime prevention approach). The paper concludes with suggestions for future research in this field