The Brombergs, who immigrated to Israel from São Paulo, Brazil in 2018, play and sing Leonard Cohen’s enduring classic song in English and Hebrew.

The event, led by the World Health Organization (WHO) and the nonprofit group Global Citizen, told the personal stories of teachers and healthcare, grocery, delivery, postal and other workers.

The San Francisco-based website is auctioning collectible cars online in real time — 50-plus a day, five days a week.

Noah Schnapp of "Stranger Things" and Seu Jorge try to cook up a recipe for unity in "Abe."

The plan for the Premier League to return next month may hit a roadblock with six clubs not so keen on the idea of giving up their remaining home games.

Home color kits and Zoom crystal readings fill the void. But underground services break the lockdown.

Israel's coronavirus patient 74, also known as Dani, posts about her experience on social media.

With theatres closed, Tal Kalai and Yuval Edelman streamed performances online – and ended up on TV.

Israel's PM has turned his chief challenger, Benny Gantz, into his chief deputy, writes Tom Bateman.

Many are returning to jobs in Israel and its settlements, where there has been a large outbreak.

The Amateur Traveler talks to Douglas Duckett about his travels to Israel and his popular travel guide to Israel. Douglas has fallen in love not just with the "holy land" but with the modern nation of Israel. We address the issue of "is it safe to travel to Israel" at this time when Israel is at war with the Palestinians in Gaza. He takes us on a virtual trip from the beaches and night life of Tel Aviv, through the working city of Haifa with the beautiful Baha'i gardens and the informative museum about the modern jewish immigration. We stop at Lake Kinneret (also known as The Sea of Galilee, also Sea of Genneseret, or Lake Tiberias) at the town of Tiberius. We make a detour to the historic site of Gamla the "Masada of the North" before turning our face toward Jerusalem. On the way to Jerusalem we stop at Megiddo (Armageddon in the bible) and the roman ruins at Beit-Shean. In Jerusalem we talk about the overwhelming religious and historic significance of the city and how some people come down with " Jerusalem syndrome". We suggest a walking tour of the city, a tour of the Mount of Olives, the holocaust memorial and the Israel museum. We also talk about the work the Jerusalem YMCA is doing to promote peace with their peace preschool that teaches Jewish and Palestinian children together.

The Amateur Travelertalks to Chaundra about her trip to Southern Israel, a barren but "stunning" land where every rock is full of history.

Hear about travel to Tel Aviv, Israel as the Amateur Traveler talks to Shimrit Elisar from diytelavivguide.com about her home city.

Hear about travel to Israel and Palestine, and particularly the world heritage sites of that region, as the Amateur Traveler talks to Gary Arndt from everything-everywhere.com about his recent visit.
Gary just finished up a trip to Israel and Palestine.

Research Event

Event participants

Research Event

Event participants

5 June 2014 , Volume 70, Number 3

The Golan Heights is home to thousands of Druze who cling on tenaciously while looking over their shoulder at the chaos in their homeland

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles

Research Event

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Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement.

Expert

The coach and rail journey app has launched a new AI voice app for automated disruption alerts

(Kudos Innovations Ltd) Kudos helps researchers maximize reach and visibility of research by opening up Kudos Pro. The platform helps showcase work to a range of target audiences, supporting researchers in fields where conferences have been cancelled -- and those with COVID-19-relevant work that needs rapid communication. Over 2,000 researchers have already signed up.

Palestinian officials said Friday that Israel is forcing banks in the occupied West Bank to close accounts held by the families of prisoners in Israeli jails to prevent the Palestinian Authority from providing stipends to them. Israel has long objected to the Palestinian Authority's payments to the families of prisoners and those killed in the conflict, including militants, saying it rewards terrorism. The Palestinians view the payments as a social safety net for those living under decades of military occupation.

Research Event

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Henry J. Pownall
May 1, 2020; 61:595-597
Commentary

Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor cell outer segments. Following absorption of a photon, the 11-cis-retinal chromophore of visual pigment in photoreceptor cells isomerizes to all-trans-retinal. To maintain photosensitivity 11-cis-retinal must be replaced. At the same time, however, all-trans-retinal has to be handled so as to prevent nonspecific aldehyde activity. Some molecules of retinaldehyde upon release from opsin are efficiently reduced to retinol. Other molecules are released into the lipid phase of the disc membrane where they form a conjugate (N-retinylidene-PE, NRPE) through a Schiff base linkage with phosphatidylethanolamine (PE). The reversible formation of NRPE serves as a transient sink for retinaldehyde that is intended to return retinaldehyde to the visual cycle. However, if instead of hydrolyzing to PE and retinaldehyde, NRPE reacts with a second molecule of retinaldehyde a synthetic pathway is initiated that leads to the formation of multiple species of unwanted bisretinoid fluorophores. We report on recently identified members of the bisretinoid family some of which differ with respect to the acyl chains associated with the glycerol backbone. We discuss processing of the lipid moieties of these fluorophores in lysosomes of retinal pigment epithelial (RPE) cells, their fluorescence characters and new findings related to light and iron-associated oxidation of bisretinoids.

Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement.

A panel of 11 judges ruled that Israeli Prime Minister Benjamin Netanyahu can form a government after reaching a deal with rival Benny Gantz.

Israel's Ministry of Defense ordered small drones for its ground forces working in urban areas, maker Rafael Advanced Defense Systems Ltd. said Monday.

Ofri Mosenzon
Aug 1, 2016; 39:S146-S153
II. Diabetes Treatment Options

A new scientific study published Monday found that global warming is fueling a destructive algal bloom that is disrupting fisheries in the Arabian sea.

Secretary of State Mike Pompeo plans to travel to Israel next week to meet with Prime Minister Benjamin Netanyahu in his first international trip since coronavirus-related restrictions were put in place.

A Smarter Balanced testing vendor has released completion rates in three states that had serious challenges giving the common-core aligned exam.

A Paris : chez Mondhare, [between 1760 and 1792]

Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf. Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness.

SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.

Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and related neurodegenerative tauopathies. Here, we conducted PET along with postmortem assays to investigate time course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female mice were analyzed in this study. We observed that radiosignals derived from [¹¹C]flumazenil, a tracer for benzodiazepine receptor, in rTg4510 mice were significantly lower than the levels in nontransgenic littermates at 2-3 months of age. In contrast, retentions of (E)-[¹¹C]ABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory, but not excitatory, synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 mice at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits. Our findings indicate that tau-induced disruption of the inhibitory synapse may be a critical trigger of progressive neurodegeneration, resulting in massive neuronal loss, and PET assessments of inhibitory versus excitatory synapses potentially offer in vivo indices for hyperexcitability and excitotoxicity early in the etiologic pathway of neurodegenerative tauopathies.

SIGNIFICANCE STATEMENT In this study, we examined the in vivo status of excitatory and inhibitory synapses in the brain of the rTg4510 tauopathy mouse model by PET imaging with (E)-[¹¹C]ABP688 and [¹¹C]flumazenil, respectively. We identified inhibitory synapse as being significantly dysregulated before brain atrophy at 2 months of age, while excitatory synapse stayed relatively intact at this stage. In line with this observation, postmortem assessment of brain tissues demonstrated selective attenuation of inhibitory synaptic constituents accompanied by the upregulation of cFos before the formation of tau pathology in the forebrain at young ages. Our findings indicate that selective degeneration of inhibitory synapse with hyperexcitability in the cortical circuit constitutes the critical early pathophysiology of tauopathy.

The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M₂ or M₄ receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.

SIGNIFICANCE STATEMENT The major source of acetylcholine in the hippocampus comes from the medial septum. Early experiments found that lesions to the MS result in the disappearance of hippocampal theta oscillation, which leads to speculation that the septo-hippocampal cholinergic projection contributing to theta oscillation. In this article, by long-term recording of MS cholinergic neurons, we found that they show a theta state-related firing pattern. However, optogenetically activating these neurons shows little effect on theta rhythm in the hippocampus. Instead, we found that activating MS cholinergic neurons during slow-wave sleep could suppress hippocampal ripple oscillations. This suppression is mediated by muscarinic M₂ and M₄ receptors.

Plague, war and politics have altered the yearly pilgrimage to Mecca throughout history

Overcoming scorching heat and little rain, experimental vineyards teach winemakers to cope with climate change