Immigrant Entrepreneurs in the Massachusetts Biotechnology Industry (2007)

Immigrant entrepreneurs are co-founders in 25.7 percent of Massachusetts Biotechnology firms. In 2006, these immigrant-founded biotechnology companies produced over $7.6 billion dollars in sales and employed over 4,000 workers. The foreign-born founders came from across the globe but in larger numbers from Europe, Canada or Asia. Their firms specialize in the most complex, risky, life science-intensive aspects of biotechnology to seek knowledge directly applicable to human health. Biotechnology is a crucial industry for Massachhusetts and the evidence strongly suggests that immigrants have been key contributors to this industry by establishing new businesses as well as bringing intellectual capital and thereby contributing significantly to the overall economic growth of the Commonwealth

Retrospective Evaluation of Clinical Experience With Intravenous Ascorbic Acid in Patients With Cancer.

BACKGROUND: Intravenous ascorbic acid (IV AA) has been used extensively in cancer patients throughout the United States. Currently, there are limited data on the safety and clinical effects of IV AA. The purpose of this study was to expand the current literature using a retrospective analysis of adverse events and symptomatic changes of IV AA in a large sample of cancer patients. METHODS: We conducted a retrospective chart review of all patients receiving IV AA for cancer at the Thomas Jefferson University Hospital over a 7-year period. We assessed all reports of adverse events, laboratory findings, and hospital or emergency department admissions. We also reviewed quality-of-life data, including fatigue, nausea, pain, appetite, and mood. RESULTS: There were 86 patients who received a total of 3034 doses of IV AA ranging from 50 to 150g. In all, 32 patients received only ascorbic acid as part of their cancer management (1197 doses), whereas 54 patients received ascorbic acid in conjunction with chemotherapy (1837 doses). The most common adverse events related to ascorbic acid were temporary nausea and discomfort at the injection site. All events reported in the ascorbic acid alone group were associated with less than 3% of the total number of infusions. Patients, overall, reported improvements in fatigue, pain, and mood while receiving ascorbic acid. CONCLUSIONS: The results of this retrospective analysis support the growing evidence that IV AA is generally safe and well tolerated in patients with cancer, and may be useful in symptom management and improving quality of life

Plastin and spectrin cooperate to stabilize the actomyosin cortex during cytokinesis

Cytokinesis, the process that partitions the mother cell into two daughter cells, requires the assembly and constriction of an equatorial actomyosin network. Different types of non-motor F-actin crosslinkers localize to the network, but their functional contribution remains poorly understood. Here, we describe a synergy between the small rigid crosslinker plastin and the large flexible crosslinker spectrin in the C. elegans one-cell embryo. In contrast to single inhibitions, co-inhibition of plastin and the βH-spectrin (SMA-1) results in cytokinesis failure due to progressive disorganization and eventual collapse of the equatorial actomyosin network. Cortical localization dynamics of non-muscle myosin II in co-inhibited embryos mimic those observed after drug-induced F-actin depolymerization, suggesting that the combined action of plastin and spectrin stabilizes F-actin in the contractile ring. An in silico model predicts that spectrin is more efficient than plastin at stabilizing the ring and that ring formation is relatively insensitive to βH-spectrin length, which is confirmed in vivo with a sma-1 mutant that lacks 11 of its 29 spectrin repeats. Our findings provide the first evidence that spectrin contributes to cytokinesis and highlight the importance of crosslinker interplay for actomyosin network integrity

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Black social media influencers engage higher percentages of Black gay and bisexual men in online outreach for HIV prevention research relative to paid ads

Background: Influencer-based social media marketing campaigns are a popular strategy to engage customers in many non-research industries (e.g., retail), but have been increasingly used in public health campaigns to reach and engage specific populations. However, few studies have directly compared the performance of influencer-based marketing with other ad strategies (e.g., paid ads) in achieving these goals. Methods: From March to September 2023, we conducted an influencer-focused marketing campaign in which we identified and partnered with predominantly Black LGBTQ + influencers in the United States South to promote engagement in our ongoing research. We then used web analytics and interest form data to compare performance of influencer posts versus paid ads over the same time period. Results: We contacted a total of 358 influencers, 20 of whom ultimately agreed to post (85% Black/African American) and made a total of 28 posts on our behalf. A significantly higher percentage of users who clicked through influencer posts were Black (40% vs. 15%), were not currently using pre-exposure prophylaxis (PrEP) (67% vs. 62%), had no history of PrEP use (78% vs. 72%), and reported higher medical mistrust (12% vs. 8%) compared to those who clicked through paid ads. The percentage of Black men who have sex with men who were at high HIV risk, who were not taking PrEP, had no history of PrEP, or were high in mistrust, were all 2–3 times higher among those who clicked through influencer posts relative to paid ads. Conclusions: Influencer-focused marketing may be a powerful tool to efficiently reach and engage high-priority and hard to reach populations

Contradictory reasoning network:an EEG and FMRI study

Contradiction is a cornerstone of human rationality, essential for everyday life and communication. We investigated electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) in separate recording sessions during contradictory judgments, using a logical structure based on categorical propositions of the Aristotelian Square of Opposition (ASoO). The use of ASoO propositions, while controlling for potential linguistic or semantic confounds, enabled us to observe the spatial temporal unfolding of this contradictory reasoning. The processing started with the inversion of the logical operators corresponding to right middle frontal gyrus (rMFG-BA11) activation, followed by identification of contradictory statement associated with in the right inferior frontal gyrus (rIFG-BA47) activation. Right medial frontal gyrus (rMeFG, BA10) and anterior cingulate cortex (ACC, BA32) contributed to the later stages of process. We observed a correlation between the delayed latency of rBA11 response and the reaction time delay during inductive vs. deductive reasoning. This supports the notion that rBA11 is crucial for manipulating the logical operators. Slower processing time and stronger brain responses for inductive logic suggested that examples are easier to process than general principles and are more likely to simplify communication. © 2014 Porcaro et al

Mechanisms underlying disorders of consciousness: Bridging gaps to move toward an integrated translational science

AIM: In order to successfully detect, classify, prognosticate, and develop targeted therapies for patients with disorders of consciousness (DOC), it is crucial to improve our mechanistic understanding of how severe brain injuries result in these disorders. METHODS: To address this need, the Curing Coma Campaign convened a Mechanisms Sub-Group of the Coma Science Work Group (CSWG), aiming to identify the most pressing knowledge gaps and the most promising approaches to bridge them. RESULTS: We identified a key conceptual gap in the need to differentiate the neural mechanisms of consciousness per se, from those underpinning connectedness to the environment and behavioral responsiveness. Further, we characterised three fundamental gaps in DOC research: (1) a lack of mechanistic integration between structural brain damage and abnormal brain function in DOC; (2) a lack of translational bridges between micro- and macro-scale neural phenomena; and (3) an incomplete exploration of possible synergies between data-driven and theory-driven approaches. CONCLUSION: In this white paper, we discuss research priorities that would enable us to begin to close these knowledge gaps. We propose that a fundamental step towards this goal will be to combine translational, multi-scale, and multimodal data, with new biomarkers, theory-driven approaches, and computational models, to produce an integrated account of neural mechanisms in DOC. Importantly, we envision that reciprocal interaction between domains will establish a virtuous cycle, leading towards a critical vantage point of integrated knowledge that will enable the advancement of the scientific understanding of DOC and consequently, an improvement of clinical practice

Using fMRI to investigate the potential cause of inverse oxygenation reported in fNIRS studies of motor imagery

© 2019 Elsevier B.V. Motor imagery (MI) is a commonly used cognitive task in brain–computer interface (BCI) applications because it produces reliable activity in motor-planning regions. However, a number of functional near-infrared spectroscopy (fNIRS) studies have reported the unexpected finding of inverse oxygenation: increased deoxyhemoglobin and decreased oxyhemoglobin during task periods. This finding questions the reliability of fNIRS for BCI applications given that MI activation should result in a focal increase in blood oxygenation. In an attempt to elucidate this phenomenon, fMRI and fNIRS data were acquired on 15 healthy participants performing a MI task. The fMRI data provided global coverage of brain activity, thus allowing visualization of all potential brain regions activated and deactivated during task periods. Indeed, fMRI results from seven subjects included activation in the primary motor cortex and/or the pre-supplementary motor area during the rest periods in addition to the expected activation in the supplementary motor and premotor areas. Of these seven subjects, two showed inverse oxygenation with fNIRS. The proximity of the regions showing inverse oxygenation to the motor planning regions suggests that inverse activation detected by fNIRS may likely be a consequence of partial volume errors due to the sensitivity of the optodes to both primary motor and motor planning regions

A Framework for Multi-Omic Prediction of Treatment Response to Biologic Therapy for Psoriasis.

Biologic therapies have shown high efficacy in psoriasis, but individual response varies and is poorly understood. To inform biomarker discovery in the Psoriasis Stratification to Optimise Relevant Therapy (i.e., PSORT) study, we evaluated a comprehensive array of omics platforms across three time points and multiple tissues in a pilot investigation of 10 patients with severe psoriasis, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used RNA sequencing to analyze mRNA and small RNA transcriptome in blood, lesional and nonlesional skin, and the SOMAscan platform to investigate the serum proteome. Using an integrative systems biology approach, we identified signals of treatment response in genes and pathways associated with TNF signaling, psoriasis pathology, and the major histocompatibility complex region. We found association between clinical response and TNF-regulated genes in blood and skin. Using a combination of differential expression testing, upstream regulator analysis, clustering techniques, and predictive modeling, we show that baseline samples are indicative of patient response to biologic therapies, including signals in blood, which have traditionally been considered unreliable for inference in dermatology. In conclusion, our pilot study provides both an analytical framework and empirical basis to estimate power for larger studies, specifically the ongoing PSORT study, which we show as powered for biomarker discovery and patient stratification