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"Lewis, Richard"
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The molecular choreography of a store-operated calcium channel
A good SOCE
Store-operated Ca
2+
entry (SOCE) is a signalling process whereby a decrease in the concentration of Ca
2+
in the endoplasmic reticulum (ER) triggers Ca
2+
influx via channels in the plasma membrane. SOCE has been detected in many types of excitable and non-excitable cells, involved in essential functions such as secretion and immunity. Despite intense interest in SOCE, its molecular basis remained elusive until recently, when genes for the ER Ca
2+
sensor and Ca
2+
release-activated Ca
2+
(CRAC) channel were identified. A molecular picture of CRAC channel activation and SOCE is now starting to emerge.
Store-operated calcium channels (SOCs) serve essential functions from secretion and motility to gene expression and cell growth. A fundamental mystery is how the depletion of Ca
2+
from the endoplasmic reticulum (ER) activates Ca
2+
entry through SOCs in the plasma membrane. Recent studies using genetic approaches have identified genes encoding the ER Ca
2+
sensor and a prototypic SOC, the Ca
2+
-release-activated Ca
2+
(CRAC) channel. New findings reveal a unique mechanism for channel activation, in which the CRAC channel and its sensor migrate independently to closely apposed sites of interaction in the ER and the plasma membrane.
Journal Article
Across the alley
Jewish Abe's grandfather wants him to be a violinist while African-American Wille's father plans for him to be a great baseball pitcher, but it turns out that the two boys are more talented when they switch hobbies.
Book
Dissecting the numbers: A detailed analysis of 23 years of mass shootings across the United States
Mass shootings (MS) represent a significant public health problem. The true extent of which remains to be established. Thus, we examined how publicly available, law enforcement and news data might serve to better characterize MS events.
MS (defined as the killing of ≥3 people in a public space excluding the shooter) in the US over 23-years, ending in 2022, were analyzed. Data included number of victims, wounded, and fatalities, firearm type, social media postings, psychiatric history, and demographics. Ratio of fatalities per wounded were stratified by weapon and compared. Rates of MS victims, wounded, and fatalities per 100 million population were stratified by year and compared over time using simple linear regression (LR).
141 MS incidents were identified. Handguns, rifles and shotguns accounted for 80.1 %, 34.8 %, and 19.1 % of incidents, respectively. Rifles accounted for significantly more (p < 0.001) victims (17.5) per incident than multiple weapons (9), handguns (6), and shotguns (6), but had a significantly lower (p = 0.002) fatality to wounded ratio (1) compared to multiple weapons (1.29), handguns (3), and shotguns (2.5). Although LR did not find a significant increase in the rate of MS wounded (0–34.5; β = 1.85, p < 0.084), it did identify a significant increase in the rate of both MS victims (2.49–56.7; β = 2.8, p = 0.029) and fatalities (2.49–22.2; β = 0.95, p < 0.0001) per 100M population from 2000 to 2022.
The rate of both MS victims and fatalities has steadily and significantly increased over the past 23-years, despite an unchanging rate of MS wounded. This discrepancy, with fatalities far outpacing wounded, underscores the current reality of MS – those shot during a MS incident are more likely to die than previously. Thus, our study helps to identify where best to focus prevention efforts and firearm policy if we hope to reduce MS-related fatalities.
•Mass shootings.•Weapon types in mass shootings.•Trends in mass shootings in the USA.
Journal Article
Jon Lewis : photographs of the California Grape Strike
\"In the winter of 1966, twenty-eight-year-old ex-marine Jon Lewis visited Delano, California, center of the California grape strike. He thought that he might stay awhile, then resume studying photography at San Francisco State University. He stayed for two years, becoming the United Farm Workers Union's semiofficial photographer and a close confidant of farmworker leader Cesar Chavez.Surviving on a picket's wage of five dollars a week, Lewis photographed twenty-four hours a day and created an insider's view of the historic and sometimes violent confrontations, mass marches, fasts, picket lines, and boycotts that forced the table-grape industry to sign the first contracts with a farm workers union. Though some of his images were published contemporaneously, most remained unseen. Historian and photographer Richard Steven Street rescues Lewis from obscurity, allowing us for the first time to see a pivotal moment in civil rights history through the lens of a passionate photographer. A masterpiece of social documentary, this work is at once the biography of a photographer, an expose of poverty and injustice, and a celebration of the human spirit\"-- Provided by publisher.
Book
Ciguatera Fish Poisoning in the Caribbean Sea and Atlantic Ocean: Reconciling the Multiplicity of Ciguatoxins and Analytical Chemistry Approach for Public Health Safety
Ciguatera is a major circumtropical poisoning caused by the consumption of marine fish and invertebrates contaminated with ciguatoxins (CTXs): neurotoxins produced by endemic and benthic dinoflagellates which are biotransformed in the fish food-web. We provide a history of ciguatera research conducted over the past 70 years on ciguatoxins from the Pacific Ocean (P-CTXs) and Caribbean Sea (C-CTXs) and describe their main chemical, biochemical, and toxicological properties. Currently, there is no official method for the extraction and quantification of ciguatoxins, regardless their origin, mainly due to limited CTX-certified reference materials. In this review, the extraction and purification procedures of C-CTXs are investigated, considering specific objectives such as isolating reference materials, analysing fish toxin profiles, or ensuring food safety control. Certain in vitro assays may provide sufficient sensitivity to detect C-CTXs at sub-ppb levels in fish, but they do not allow for individual identification of CTXs. Recent advances in analysis using liquid chromatography coupled with low- or high-resolution mass spectrometry provide new opportunities to identify known C-CTXs, to gain structural insights into new analogues, and to quantify C-CTXs. Together, these methods reveal that ciguatera arises from a multiplicity of CTXs, although one major form (C-CTX-1) seems to dominate. However, questions arise regarding the abundance and instability of certain C-CTXs, which are further complicated by the wide array of CTX-producing dinoflagellates and fish vectors. Further research is needed to assess the toxic potential of the new C-CTX and their role in ciguatera fish poisoning. With the identification of C-CTXs in the coastal USA and Eastern Atlantic Ocean, the investigation of ciguatera fish poisoning is now a truly global effort.
Journal Article
Alice's adventures in Wonderland
Presents extracts from the story in which Alice experiences unusual adventures with a variety of nonsensical characters after falling down a rabbit hole, plus an introduction and notes on the legacy of the story, on a single, two-sided, accordion-folded sheet with pop-up illustrations.
Book
Autoantibodies to Agrin in Myasthenia Gravis Patients
To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ.
Journal Article