Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.

The cerebellum influences motor control through Purkinje target neurons, which transmit cerebellar output. Such output is required, for instance, for larval zebrafish to learn conditioned fictive swimming. The output cells, called eurydendroid neurons (ENs) in teleost fish, are inhibited by Purkinje cells and excited by parallel fibers. Here, we investigated the electrophysiological properties of glutamatergic ENs labeled by the transcription factor olig2. Action potential firing and synaptic responses were recorded in current clamp and voltage clamp from olig2⁺ neurons in immobilized larval zebrafish (before sexual differentiation) and were correlated with motor behavior by simultaneous recording of fictive swimming. In the absence of swimming, olig2⁺ ENs had basal firing rates near 8 spikes/s, and EPSCs and IPSCs were evident. Comparing Purkinje firing rates and eurydendroid IPSC rates indicated that 1-3 Purkinje cells converge onto each EN. Optogenetically suppressing Purkinje simple spikes, while preserving complex spikes, suggested that eurydendroid IPSC size depended on presynaptic spike duration rather than amplitude. During swimming, EPSC and IPSC rates increased. Total excitatory and inhibitory currents during sensory-evoked swimming were both more than double those during spontaneous swimming. During both spontaneous and sensory-evoked swimming, the total inhibitory current was more than threefold larger than the excitatory current. Firing rates of ENs nevertheless increased, suggesting that the relative timing of IPSCs and EPSCs may permit excitation to drive additional eurydendroid spikes. The data indicate that olig2⁺ cells are ENs whose activity is modulated with locomotion, suiting them to participate in sensorimotor integration associated with cerebellum-dependent learning.

SIGNIFICANCE STATEMENT The cerebellum contributes to movements through signals generated by cerebellar output neurons, called eurydendroid neurons (ENs) in fish (cerebellar nuclei in mammals). ENs receive sensory and motor signals from excitatory parallel fibers and inhibitory Purkinje cells. Here, we report electrophysiological recordings from ENs of larval zebrafish that directly illustrate how synaptic inhibition and excitation are integrated by cerebellar output neurons in association with motor behavior. The results demonstrate that inhibitory and excitatory drive both increase during fictive swimming, but inhibition greatly exceeds excitation. Firing rates nevertheless increase, providing evidence that synaptic integration promotes cerebellar output during locomotion. The data offer a basis for comparing aspects of cerebellar coding that are conserved and that diverge across vertebrates.

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Abstract: This articles reviews the Court of Appeal decision in Serafin v Malkiewicz reversing the dismissal at first instance of a libel claim relating to an article which made serious allegations about the claimant.  The ruling makes clear th...

Progression from the initial vascular response upon hyperglycemia to a proliferative stage with neovacularizations is the hallmark of proliferative diabetic retinopathy. Here, we report on the novel diabetic pdx1^–/– zebrafish mutant as a model for diabetic retinopathy that lacks the transcription factor pdx1 through CRISPR-Cas9–mediated gene knockout leading to disturbed pancreatic development and hyperglycemia. Larval pdx1^–/– mutants prominently show vasodilation of blood vessels through increased vascular thickness in the hyaloid network as direct developmental precursor of the adult retinal vasculature in zebrafish. In adult pdx1^–/– mutants, impaired glucose homeostasis induces increased hyperbranching and hypersprouting with new vessel formation in the retina and aggravation of the vascular alterations from the larval to the adult stage. Both vascular aspects respond to antiangiogenic and antihyperglycemic pharmacological interventions in the larval stage and are accompanied by alterations in the nitric oxide metabolism. Thus, the pdx1^–/– mutant represents a novel model to study mechanisms of hyperglycemia-induced retinopathy wherein extensive proangiogenic alterations in blood vessel morphology and metabolic alterations underlie the vascular phenotype.

Nayeli G. Reyes-Nava, Hung-Chun Yu, Curtis R. Coughlin II, Tamim H. Shaikh, and Anita M. Quintana

We used whole-exome sequencing (WES) to determine the genetic etiology of a patient with a multi-system disorder characterized by a seizure phenotype. WES identified a heterozygous de novo missense mutation in the GABRA1 gene (c.875C>T). GABRA1 encodes the alpha subunit of the gamma-aminobutyric acid receptor A (GABA_AR). The GABA_AR is a ligand gated ion channel that mediates the fast inhibitory signals of the nervous system, and mutations in the subunits that compose the GABA_AR have been previously associated with human disease. To understand the mechanisms by which GABRA1 regulates brain development, we developed a zebrafish model of gabra1 deficiency. gabra1 expression is restricted to the nervous system and behavioral analysis of morpholino injected larvae suggests that the knockdown of gabra1 results in hypoactivity and defects in the expression of other subunits of the GABA_AR. Expression of the human GABRA1 protein in morphants partially restored the hypomotility phenotype. In contrast, the expression of the c.875C>T variant did not restore these behavioral deficits. Collectively, these results represent a functional approach to understand the mechanisms by which loss-of-function alleles cause disease.

As the COVID-19 pandemic continues, many healthcare facilities around the world are inundated with critically ill patients, and resources such as equipment and staff are stretched thin. Shortages of critical equipment, such as ventilators, can mean the difference between life and death for patients, and the need to keep critically ill patients comfortable and alive […]

Accepting the futility of genres, of boxing songs into different compartments like stacked products in supermarket shelves, seems to be at the forefront of Rafiq Bhatia's musical endeavour. The 30-year-old American of Indian descent is the guitarist for a New York-based indie outfit called Son Lux. But it's his recent solo album, Breaking English, which makes the listener really question the need for musical boundaries, of sticking labels to a composition as if it's packaged meat.

The title track of the album, for instance, is not jazz, is not electronica, is not lounge, but all of these generic classifications rolled into one lush sound with a coherent narrative, where Bhatia's melancholic guitar plays the role of the protagonist. Each sonic detail in the track is well-defined, to the point where even though fellow Son Lux member Ian Chang's drum beats seem dissonant, they fit like a glove into the overall musical fabric. Bhatia describes this sensibility when he tells us over the phone from Berlin, where he's on tour, "Ryan (Lott, the vocalist for Son Lux) would say that instead of building a house, designing a room and then placing a chair in it, why don't we start with the chair first, and then design the room around it before building the house. There is a theory in poetry called organicism, where the poet lets each individual verse define the form that the poem will take. That is kind of similar to what I'm trying to do with my music."

He further explains his musical process when he narrates a story about one of his influences, Sam Rivers, the late American jazz great. "I've read that he would attend the concerts of all his peers, and purposely study their music to understand what they were trying to do. But this wasn't to replicate what they were playing. Instead, it was to consciously avoid it. Similarly, John Coltrane took the music of his predecessors and retooled the entire musical vocabulary keeping a similar underlying foundation, but with new pathways built on top of it," he says, giving us an indication of how he doesn't hesitate to flush rule books down the toilet.

Hybridity, in fact, lies at the core of Bhatia's creative evolution. The basis for this, he says, might well be his mixed identity. Born in North Carolina, he has never really fit in to any particular community. For, even though his parents are of Gujarati origin, they grew up in Tanzania, before moving to London and then finally to the US. So, while his brown skin stood out among the white kids in his school, he didn't feel completely at home among the Indian community either. "Everybody thinks that I am something else. So, my music is a result of a need to express my identity. It's a form of therapy at some level, because it's also a way of accepting who I am," he says.

He adds that this therapy started early. When he was about eight or nine, the older desi kids in Bhatia's neighbourhood would pick him up in a car and stop at a parking lot, listening to the hip-hop albums that became one of his earliest influences. Was he drawn to them because of the political overtones that such songs often embody? "Not really," he answers, adding, "I was only in the third grade at the time, and I couldn't even understand the words. So it was the musicality that I fell for. But the deeper question is, why were a bunch of brown kids sitting in a car in a parking lot and empathising with hip-hop music? What is it that was drawing them to the words? So you see, it's difficult to disentangle the politics from the music."

It follows thus that an intertwining of politics and music sometimes features in his own compositions. For example, Hoods Up, a complex instrumental piece, drew its inspiration from Trayvon Martin, a black teenager who was cruelly shot down because of a case of mistaken identity. The guitarist says, "I feel some amount of compulsion to express my [political] ideas. But sometimes, it's easy to get carried away with being overtly political because there is so much to be angry about, and often the responsibility falls on artistes to emphasise it. So I would say that politics is a general part of what inspires my music, because there are so many other facets of my personality that also make their way in."

Essentially, then, what Bhatia wants to keep doing is create genre-defying tracks where attention to detail is of paramount importance. "When you take the details and all the generalities of music for granted, that's when your songs start sounding more like other people's music. That doesn't mean you can't make great tracks. It's just that the less you consider those things, the less is the chance that you will make music that departs from convention. The flip side is that when you think actively about each decision, and each one comes from a place of individuality, it becomes hard to find a coherent logic that ties all those things together. And that ends up being the riddle that I am constantly trying to solve with my music."

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Haitham with Shah Rukh Khan on the sets of Dil Hai Hindustani where the two sang SRK’s chartbuster Jabra Fan

When we meet Haitham Mohammed Rafi inside the dimly-lit sets of a popular music reality show, he stands out from those sitting beside him. The white of his traditional dishdasha and the colourful turban — called the massar — make him look like an anomaly. The 23-year-old appears to be closely observing his fellow singer — a girl half his age — who is on stage and singing the famous DDLJ-towel song, 'Mere Khwabon Mein Jo Aaye,' when we raise our hand and call for his attention. There is instant recognition.

"Wallah!" he yells out in Arabic. "How come, you here?" he goes on, in his Middle-Eastern accent.

It has been three years since we first met Haitham. The last time it was in his hometown Muscat, the capital city of the Sultanate of Oman. "I will sing in Bollywood, someday, Inshallah!" he had then rapped, much to the amusement of this correspondent. At the time, we had wished him luck, without mocking his expectations or pointing out the risks.

Last week, when a video of filmmaker Karan Johar sitting in stunned silence after Haitham’s performance of Naina Thag Lenge, went viral on Arab social media, this writer was glad she had kept mum then.

Haitham, an Omani national, has just made it in the final 11 of the first season of music reality show Dil Hai Hindustani. Being an Arab, has only worked in his favour. For the judges, Johar, Badshah, Shalmali Kholgade and Shekhar Ravjiani (of Vishal-Shekhar fame), the first question on their mind was, “Can an Arab sing in Hindi?”

"Okay, maybe!" "But, that good!"

"I have Mohammed Rafi’s blessings," Haitham jokes. Not like, we hadn’t been meaning to ask him the story behind his namesake. Haitham al Balushi takes his middle name, Mohammed Rafi, from his father, who was surprisingly christened by the veteran Hindi singer himself. "Though Omani, my grandfather was a huge fan of Mohammed Rafi," he recounts. “When my father was born, Rafi saab was performing in Bahrain. My grandfather, who was working there, went for the show and managed to have a quick chat with him backstage," he says, adding, “He told Rafi saab, I want you to name my newborn.” The rest, as the Balushi family recalls, is history.

Until seven months ago, Haitham worked as a personal banker with a leading national bank in Muscat. “It was so boring. I hated going to work...it was suffocating," he says. Unable to take it anymore, Haitham put in his papers, and ferociously started looking for opportunities to sing. "I wanted to pursue my passion," he says. We ask him what that is? And, pat comes the reply, "I want to become the first Arab playback singer and composer in Bollywood." Haitham has been harbouring that dream since he was 11.

In Oman, Haitham says, there is no concept of vocal training. "If you're a good singer, you're a good singer." His only source of Bollywood music was audiocassettes and CDs as a child, and later YouTube. "So, when I told my Omani friends that I wanted to become a singer, they laughed. They said, 'You can’t make it big in India…it is so tough'."

On an Indian friend’s advise, he started listening to a lot of ghazals. "I was told that it would help me get my nuances and accent right," he says. His favourite ghazal singers are Jagjit Singh and Rahat Fateh Ali Khan. But, that's how Haitham’s Bollywood dreams first took flight.

In 2012, he became the first Omani to win Muscat Idol, which sees participants mostly from the Indian Diaspora. From there on, due to dearth of a great body of work, Haitham started composing music for Omani TV shows. “But, I realised that I wasn’t enjoying Arabic music. Each time, I sang in Hindi, I was happier,” he says. Of the 500 songs he has composed, 450 were in Hindi. “My mum knew I wasn’t meant for Oman. So, she kept pushing me to try my luck at Indian reality shows,” he says. He tried thrice and failed. The fourth time, he decided to think practically and opted for 'The Voice Ahla Sawt', the Arabic version of the international music show. “Even there, I could not fit in,” he says. This December, after five years of working towards his dream, he got the call. And, that too, from India.

Here, he is still just another contender at the show. But, back home, things have changed for Haitham. After a video of his performance went viral, Omanis in Muscat, who he claims love Hindi cinema, have gone into an overdrive. “I’ve already signed 13 shows in Muscat and Dubai,” he says. “My friends are buying the Indian digital channels, just to watch my show.”

"I think it's a proud moment for my country," Haitham says. Just as we end, he gets his cellphone out, and shows us a photograph of his, clicked with Shah Rukh Khan, where the two are facing each other, striking the latter's signature pose. “India has already opened its arms to me," he gushes.

Poşta Română a redeschis, astăzi, de Ziua Europei, trei rute noi pentru îndrumarea traficului poştal internaţional cu Ungaria, Bulgaria şi Serbia, pe cale rutieră, a anunţat operatorul poştal într-un comunicat de presă, preluat de AGERPRES.

The post Poșta Română a redeschis rutele pentru traficul poștal cu Bulgaria, Ungaria și Serbia appeared first on Forbes.ro.

Rotch Library - N6496.3.S9 Z876 2018

Müller-Brockmann, Josef, 1914-1996, author

Bosshard, Hans Rudolph, 1929-

Online Resource

Taras Shevchenko National University of Kyiv

Firenze University Press

Novosibirsk : Izd-vo In-ta arkheologii i ėtnografii SO RAN

The College of Veterinary Medicine, University of Mosul

The College of Veterinary Medicine, University of Mosul

Online Resource

Hayden Library - Q175.5.S3234 2018

Online Resource

Online Resource

Milano : Springer Milan, 2006

Milano : Springer, [2007]

[Milano] : Springer, 2006

Milano : Springer Milan, 2006

Rotch Library - BP190.5.H44 Z35 2017

Rotch Library - DR1667.T67 2017

Rotch Library - Z675.A82 H577 2016