Land Protection and Habitat Restoration as Catalysts for Sustained Community Engagement at the Roslindale Wetlands Urban Wild

The Roslindale Wetlands “Urban Wild,” a 10-acre forested wetland in the heart of Boston, Massachusetts, is the backdrop for a compelling story of land preservation and habitat restoration as primary drivers for sustained community engagement. Originally identified for residential development, this patchwork of City and private land was long neglected and degraded by incompatible adjacent development and illegal dumping. In 2005, the community group Roslindale Wetlands Task Force (RWTF) was formed to start the long, gradual process of cleaning up and advocating for full preservation of the site. However, between 2019 and 2023, an alignment of several strategic joint planning ventures between the RWTF, the City of Boston, and Mass Audubon accelerated efforts and culminated in a giant leap forward. By 2023, the majority of the site was permanently protected and was ecologically restored through a $1 million City capital renovation investment. These milestone achievements, in turn, have recharged long-term community organizing and site stewardship efforts and contributed to a wider embrace of this nature park by Bostonians

Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions

All the Brain\u27s a Stage for Serotonin: The Forgotten Story of Serotonin Diffusion across Cell Membranes

In the conventional model of serotonin neurotransmission, serotonin released by neurons in the midbrain raphe nuclei exerts its actions on forebrain neurons by interacting with a large family of post-synaptic receptors. The actions of serotonin are terminated by active transport of serotonin back into the releasing neuron, which is mediated by the serotonin reuptake transporter (SERT). Because SERT is expressed pre-synaptically and is widely thought to be the only serotonin transporter in the forebrain, the conventional model does not include serotonin transport into post-synaptic neurons. However, a large body of evidence accumulating since the 1970s has shown that serotonin, despite having a positive charge, can cross cell membranes through a diffusion-like process. Multiple low-affinity, high-capacity, sodium-independent transporters, widely expressed in the brain, allow the carrier-mediated diffusion of serotonin into forebrain neurons. The amount of serotonin crossing cell membranes through this mechanism under physiological conditions is considerable. Most prominent textbooks fail to include this alternative method of serotonin uptake in the brain, and even most neuroscientists are unaware of it. This failure has limited our understanding of a key regulator of serotonergic neurotransmission, impeded research on the potential intracellular actions of serotonin in post-synaptic neurons and glial cells, and may have impeded our understanding of the mechanism by which antidepressant medications reduce depressive symptoms

Identification of a Core Amino Acid Motif within the α Subunit of GABAARs that Promotes Inhibitory Synaptogenesis and Resilience to Seizures

The fidelity of inhibitory neurotransmission is dependent on the accumulation of γ-aminobutyric acid type A receptors (GABAARs) at the appropriate synaptic sites. Synaptic GABAARs are constructed from α(1-3), β(1-3), and γ2 subunits, and neurons can target these subtypes to specific synapses. Here, we identify a 15-amino acid inhibitory synapse targeting motif (ISTM) within the α2 subunit that promotes the association between GABAARs and the inhibitory scaffold proteins collybistin and gephyrin. Using mice in which the ISTM has been introduced into the α1 subunit (Gabra1-2 mice), we show that the ISTM is critical for axo-axonic synapse formation, the efficacy of GABAergic neurotransmission, and seizure sensitivity. The Gabra1-2 mutation rescues seizure-induced lethality in Gabra2-1 mice, which lack axo-axonic synapses due to the deletion of the ISTM from the α2 subunit. Taken together, our data demonstrate that the ISTM plays a critical role in promoting inhibitory synapse formation, both in the axonic and somatodendritic compartments

Primary Care Expenditures before the Onset of Alzheimer's Disease

Objective: To investigate primary care expenditures in the period before diagnosis of AD. Methods: In a population-based sample of Medicare enrollees in New York City, person-level 1996 Medicare claims, summed over primary care encounters, were examined for people who developed AD in 1997 to 1998 and those who did not. Results: People who developed AD were more likely to use Medicare outpatient and ambulatory care 1 to 2 years before diagnosis. Compared with respondents who did not develop AD, the excess cost for men was $1,167 (85$239 (26% higher). Among elderly people ≥75 years in the United States, the prodromal period of AD was associated with an excess Medicare-based primary care cost of $128.5 to$194.7 million. Conclusion: In addition to huge costs associated with AD after diagnosis, prediagnosis costs are an unrecognized source of expenditures related to the disease

The perturbations ϕ2,1\phi_{2,1} and ϕ1,5\phi_{1,5} of the minimal models M(p,p′)M(p,p') and the trinomial analogue of Bailey's lemma

We derive the fermionic polynomial generalizations of the characters of the integrable perturbations $\phi_{2,1}$ and $\phi_{1,5}$ of the general minimal $M(p,p')$ conformal field theory by use of the recently discovered trinomial analogue of Bailey's lemma. For $\phi_{2,1}$ perturbations results are given for all models with $2p>p'$ and for $\phi_{1,5}$ perturbations results for all models with ${p'\over 3}<p< {p'\over 2}$ are obtained. For the $\phi_{2,1}$ perturbation of the unitary case $M(p,p+1)$ we use the incidence matrix obtained from these character polynomials to conjecture a set of TBA equations. We also find that for $\phi_{1,5}$ with $2<p'/p < 5/2$ and for $\phi_{2,1}$ satisfying $3p<2p'$ there are usually several different fermionic polynomials which lead to the identical bosonic polynomial. We interpret this to mean that in these cases the specification of the perturbing field is not sufficient to define the theory and that an independent statement of the choice of the proper vacuum must be made.Comment: 34 pages, 15 figures, harvmac. References added and the TBA conjecture refine

A contracting circumbinary molecular ring with an inner cavity of about 140 AU around Ori 139-409

Sensitive and subarcsecond resolution ($\sim$ 0.7\arcsec) CH$_3$OH(7$_{-2,6}$ $\to$ 6$_{-2,5}$) line and 890 $\mu$m continuum observations made with the Submillimeter Array (SMA) towards the hot molecular circumbinary ring associated with the young multiple star Ori 139-409 are presented. The CH$_3$OH(7$_{-2,6}$ - 6$_{-2,5}$) emission from the ring is well resolved at this angular resolution revealing an inner cavity with a size of about 140 AU. A LTE model of a Keplerian disk with an inner cavity of the same size confirms the presence of this cavity. Additionally, this model suggests that the circumbinary ring is contracting with a velocity of V$_{inf}$ $\sim$ 1.5 km s$^{-1}$ toward the binary central compact circumstellar disks reported at a wavelength of 7 mm. {\bf The inner central cavity seems to be formed by the tidal effects of the young stars in the middle of the ring.} The ring appears to be not a stationary object. Furthermore, the infall velocity we determine is about a factor of 3 slower than the free-fall velocity corresponding to the dynamical mass. This would correspond to a mass accretion rate of about 10$^{-5}$ M$_\odot$/yr. We found that the dust emission associated with Ori 139-409 appears to be arising from the circumstellar disks with no strong contribution from the molecular gas ring. A simple comparison with other classical molecular dusty rings (e.g. GG Tau, UZ Tau, and UY Aur) suggests that Ori 139-409 could be one of the youngest circumbinary rings reported up to date. Finally, our results confirm that the circumbinary rings are actively funneling fresh gas material to the central compact binary circumstellar disks, i.e. to the protostars in the very early phases of their evolution.Comment: Accepted by MNRA

Hamiltonians for the Quantum Hall Effect on Spaces with Non-Constant Metrics

The problem of studying the quantum Hall effect on manifolds with nonconstant metric is addressed. The Hamiltonian on a space with hyperbolic metric is determined, and the spectrum and eigenfunctions are calculated in closed form. The hyperbolic disk is also considered and some other applications of this approach are discussed as well.Comment: 16 page