Recommendations for Improving Firearms Vetting in Massachusetts

The United States is in a state of conflict over the ability to obtain firearms as well as their use in highly publicized mass shootings. On December 14, 2012, Adam Lanza obtained several firearms that were lawfully owned by his mother, but were improperly secured. Lanza killed his mother that morning and then drove a short distance to the Sandy Hook Elementary School in Newtown, Connecticut where he murdered twenty-six people, many of whom were small children. Lanza eventually turned a gun on himself before being confronted by responding officers. Though mass shootings are often headlines in this country, the vast majority of misused firearms by the mentally ill are tragically used in suicide. The lessons of these examples must be used to augment current firearms policy in an effort to reduce the availability of firearms to those suffering with afflictions that make them ill equipped to have access to them. Though the Commonwealth of Massachusetts asks pointed questions in these areas regarding the fitness of the potential license holder, it collects no data whatsoever regarding other full-time household members where a firearm may be kept, nor what measures the licensee takes to ensure its security. This Article illustrates a policy, grounded in facilitative principles, designed to reduce access to firearms by those mentally incapable of handling them or those with current substance addictions. Key components to the solution’s success should rely on increased vetting of the licensee’s environment and where lawfully owned firearms will be stored, in combination with assessing the risk factors of having been hospitalized for mental health, drug dependence, or alcohol dependence. This recommendation is merely an expansion of questions already used in the current Massachusetts firearms licensing application and would produce additional factors that a licensing official may consider when determining the suitability of an applicant. It is important to note that this would not be an outright prohibition for a licensee, which would likely be constitutionally impermissible. This Article concludes by reemphasizing the importance of giving licensing officials more information to consider in an effort to lower the risk of lawfully owned firearms ending up in the hands of the mentally ill or violent

Rocaglates induce gain-of-function alterations to eIF4A and eIF4F

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5' leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA.P50 GM067041 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHSPublished versio

The study protocol for a pseudo-randomised pre-post designed controlled intervention trial to study the effects of a 7-week cooking program on self-efficacy and biomarkers of health: the ECU lifestyle and biomarkers get connected study (ECULABJMOF) including the Jamie’s Ministry of Food WA participant experience

Background: Australia, like other nations, has experienced a shift in dietary patterns away from home cooking of nutritious foods, towards a reliance on pre-prepared convenience meals. These are typically energy-dense, nutrient-poor and contribute to the rising prevalence of obesity and chronic disease burden. The aims of this study were to evaluate whether a community-based cooking program instigated a change to participants’ skills, attitudes, knowledge, enjoyment and satisfaction of cooking and cooking confidence (self-efficacy). Methods: The pseudo-random, pre-post study design consisted of an intervention and a control group. Participant recruitment and group allocation was based on their program start dates. Intervention participants were surveyed three times (baseline, 7 weeks and 6 months) and the control group were surveyed at baseline and 5 weeks. All participants were registered via an online website and were 18 years or over. Upon consent, participants were offered four levels of commitment, defined by different assessments. The minimum participation level included an online survey and levels 2, 3 and 4 involved attendance at a clinic with increasing functional, anthropometric and biomarker measurements. Primary endpoints were participants’ cooking confidence as a proxy for self-efficacy. Secondary endpoints were dietary intake, physical activity levels, body composition, anthropometry, blood, urine and faecal biomarkers of systemic, physical and mental health. Discussion: The community cooking program provided participants with information and advice on food sourcing, preparation and nutrition to improve home cooking skills. The study was designed to explore whether food literacy programs are efficacious in improving participant physical health and well-being in order to combat the rise in obesity and diet-related disease. It will support future use of public health cooking program initiatives aimed at improving food literacy, self-efficacy and physical and mental health. The extensive data collected will inform future research into the relationship between diet, the gut-microbiota and human health

Mass Activated Droplet Sorting (MADS) Enables Highâ Throughput Screening of Enzymatic Reactions at Nanoliter Scale

Microfluidic droplet sorting enables the highâ throughput screening and selection of waterâ inâ oil microreactors at speeds and volumes unparalleled by traditional wellâ plate approaches. Most such systems sort using fluorescent reporters on modified substrates or reactions that are rarely industrially relevant. We describe a microfluidic system for highâ throughput sorting of nanoliter droplets based on direct detection using electrospray ionization mass spectrometry (ESIâ MS). Droplets are split, one portion is analyzed by ESIâ MS, and the second portion is sorted based on the MS result. Throughput of 0.7â samplesâ sâ 1 is achieved with 98â % accuracy using a selfâ correcting and adaptive sorting algorithm. We use the system to screen â 15â 000â samples in 6â h and demonstrate its utility by sorting 25â nL droplets containing transaminase expressed in vitro. Labelâ free ESIâ MS droplet screening expands the toolbox for droplet detection and recovery, improving the applicability of droplet sorting to protein engineering, drug discovery, and diagnostic workflows.A microfluidic system for sorting nanoliter droplets based on mass spectrometry is presented. Fully automated, labelâ free sorting at 0.7â samplesâ sâ 1 is achieved with 98â % accuracy. In vitro transcription and translation (ivTT) of a transaminase enzyme in ca.â 25â nL samples is demonstrated and samples are sorted on the basis of enzyme activity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154315/1/anie201913203.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154315/2/anie201913203-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154315/3/anie201913203_am.pd

Mass Activated Droplet Sorting (MADS) Enables Highâ Throughput Screening of Enzymatic Reactions at Nanoliter Scale

Microfluidic droplet sorting enables the highâ throughput screening and selection of waterâ inâ oil microreactors at speeds and volumes unparalleled by traditional wellâ plate approaches. Most such systems sort using fluorescent reporters on modified substrates or reactions that are rarely industrially relevant. We describe a microfluidic system for highâ throughput sorting of nanoliter droplets based on direct detection using electrospray ionization mass spectrometry (ESIâ MS). Droplets are split, one portion is analyzed by ESIâ MS, and the second portion is sorted based on the MS result. Throughput of 0.7â samplesâ sâ 1 is achieved with 98â % accuracy using a selfâ correcting and adaptive sorting algorithm. We use the system to screen â 15â 000â samples in 6â h and demonstrate its utility by sorting 25â nL droplets containing transaminase expressed in vitro. Labelâ free ESIâ MS droplet screening expands the toolbox for droplet detection and recovery, improving the applicability of droplet sorting to protein engineering, drug discovery, and diagnostic workflows.Ein Mikrofluidiksystem zur Sortierung von Nanolitertröpfchen basierend auf Massenspektrometrie erreicht eine vollautomatische markierungsfreie Sortierung bei 0.7 Probenâ sâ 1 mit 98â % Genauigkeit. Die Inâ vitroâ Transkription und â Translation (ivTT) eines Transaminaseâ Enzyms in Proben von etwa 25â nL wird demonstriert, und die Proben werden nach ihrer Enzymaktivität sortiert.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154446/1/ange201913203-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154446/2/ange201913203.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154446/3/ange201913203_am.pd

T granules in human platelets function in TLR9 organization and signaling

Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the T granule. TLR9 colocalizes with protein disulfide isomerase and is associated with either VAMP 7 or VAMP 8, which regulates its distribution in PLTs on contact activation (spreading). Preincubation of PLTs with type IV collagen specifically increased TLR9 and CD62P surface expression and augmented oligodeoxynucleotide (ODN) sequestration and PLT clumping upon addition of bacterial/viral ODNs. Collectively, this paper (a) tracks TLR9 to a new intracellular compartment in PLTs and (b) describes a novel mechanism of TLR9 organization and signaling in human PLTs

Using a New Odour-Baited Device to Explore Options for Luring and Killing Outdoor-Biting Malaria Vectors: A Report on Design and Field Evaluation of the Mosquito Landing Box.

Mosquitoes that bite people outdoors can sustain malaria transmission even where effective indoor interventions such as bednets or indoor residual spraying are already widely used. Outdoor tools may therefore complement current indoor measures and improve control. We developed and evaluated a prototype mosquito control device, the 'Mosquito Landing Box' (MLB), which is baited with human odours and treated with mosquitocidal agents. The findings are used to explore technical options and challenges relevant to luring and killing outdoor-biting malaria vectors in endemic settings. Field experiments were conducted in Tanzania to assess if wild host-seeking mosquitoes 1) visited the MLBs, 2) stayed long or left shortly after arrival at the device, 3) visited the devices at times when humans were also outdoors, and 4) could be killed by contaminants applied on the devices. Odours suctioned from volunteer-occupied tents were also evaluated as a potential low-cost bait, by comparing baited and unbaited MLBs. There were significantly more Anopheles arabiensis, An. funestus, Culex and Mansonia mosquitoes visiting baited MLB than unbaited controls (P<=0.028). Increasing sampling frequency from every 120 min to 60 and 30 min led to an increase in vector catches of up to 3.6 fold (P<=0.002), indicating that many mosquitoes visited the device but left shortly afterwards. Outdoor host-seeking activity of malaria vectors peaked between 7:30 and 10:30pm, and between 4:30 and 6:00am, matching durations when locals were also outdoors. Maximum mortality of mosquitoes visiting MLBs sprayed or painted with formulations of candidate mosquitocidal agent (pirimiphos-methyl) was 51%. Odours from volunteer occupied tents attracted significantly more mosquitoes to MLBs than controls (P<0.001). While odour-baited devices such as the MLBs clearly have potential against outdoor-biting mosquitoes in communities where LLINs are used, candidate contaminants must be those that are effective at ultra-low doses even after short contact periods, since important vector species such as An. arabiensis make only brief visits to such devices. Natural human odours suctioned from occupied dwellings could constitute affordable sources of attractants to supplement odour baits for the devices. The killing agents used should be environmentally safe, long lasting, and have different modes of action (other than pyrethroids as used on LLINs), to curb the risk of physiological insecticide resistance

MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses

Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N = 10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase (www.facebase.org, https://doi.org/10.25550/3-HXMC) and GitHub (https://github.com/jaydevine/MusMorph)

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN