Molecular genetics of familial hypercholesterolemia in Israel

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by a multitude of low density lipoprotein receptor (LDL-R) mutations. The purpose of the current investigation was to define the spectrum of mutations causing FH in Israel and determine their relative distribution among diverse origin groups. A total of 193 FH families were recruited in Israel, 54 of them through the MED PED (Make Early Diagnosis Prevent Early Death) FH program. Molecular analysis of the LDL-R using single-strand conformation polymorphism (SSCP) or denaturing gradient gel electrophoresis (DGGE) or both has been completed in 95 index cases. This analysis resulted in the identification of 15 LDL receptor mutations, including 7 novel mutations (del 197, C308G, R385W, splice junction mutation of intron 14, del 328, del 502–505, stop 10, del 165), that were present in 49 index cases (52%). The 15 mutations are mapped to three known functional domains of the receptor (7 in the LDL-binding region, 7 in the epidermal growth factor precursor homology region and 1 in the membrane-spanning region). Screening for the identified mutations in the remaining 98 index cases enabled the molecular diagnosis of 31 additional cases. It is therefore concluded that 80 out of 193 index cases (41%) harbor 1 of the 15 mutations described here. Three mutations – del₁₉₇ (FH-Lithuania), D147H (FH-Sephardic), and stop₆₆₀ (Lebanese allele) – were found in a total of 66 index cases (34%); these may be regarded as founder mutations in the three respective origin groups. In conclusion, in Israel molecular heterogeneity at the LDL receptor gene locus reflects the ethnic distribution of its origin groups. The results of the present investigation provide valuable diagnostic tools for a subset of the Israeli patients with FH who are at high risk for atherosclerosis and its complications. Received: 1 February 1996 / Revised: 22 May 1996     

A deep nursery for juveniles of the zebra angelfish <Emphasis Type="Italic">Genicanthus caudovittatus</Emphasis>

Juveniles of many coral reef fish species are thought to either follow the same bathymetric distribution patterns as the adults, or to occupy shallower waters. However, our knowledge base suffers a dearth of data from the deep reefs (>40 m). In a recent survey of the deep reefs of the northern Gulf of Aqaba (<65 m), we examined the bathymetric distribution of 26 diurnal zooplanktivorous species. In sharp contrast to the general trend known from the literature and from this research, the abundance of juvenile zebra angelfish, Genicanthus caudovittatus, peaked at deeper waters (60–65 m) compared with the adults (30 m). This suggests that the deeper reefs may serve as nursery grounds for the zebra angelfish. Peak juvenile abundance coincided with relatively low predator abundances. This raises the question, which factors constrain the bathymetric distribution of the remaining species. Our findings stress the potential importance of deep coral reef research for understanding the ecological patterns and processes that govern reef community structure.     

Maturation of the neonatal oral mucosa involves unique epithelium-microbiota interactions

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Fluorescence for biological logic gates

Biological logic gates are smart probes able to respond to biological conditions in behaviors similar to computer logic gates, and they pose a promising challenge for modern medicine. Researchers are creating many kinds of smart nanostructures that can respond to various biological parameters such as pH, ion presence, and enzyme activity. Each of these conditions alone might be interesting in a biological sense, but their interactions are what define specific disease conditions. Researchers over the past few decades have developed a plethora of stimuli‐responsive nanodevices, from activatable fluorescent probes to DNA origami nanomachines, many explicitly defining logic operations. Whereas many smart configurations have been explored, in this review we focus on logic operations actuated through fluorescent signals. We discuss the applicability of fluorescence as a means of logic gate implementation, and consider the use of both fluorescence intensity as well as fluorescence lifetime.     

Discrete limbal epithelial stem cell populations mediate corneal homeostasis and wound healing

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Proteolysis of human C-reactive protein by neutrophil-derived lysosomal enzymes generates peptides which modulate neutrophil function: Implication to the anti-inflammatory mechanism

Summary Proteolysis of human C-reactive protein (CRP) by lysosomal enzymes derived from human neutrophils is shown to yield short peptides capable of modulating the production of superoxide ions by stimulated human neutrophils. Thus, fractionation of trichloroacetic acid-soluble digestion mixtures by HPLC yielded the following peptides: Ser-Tyr (1), Gly-Tyr (2), Phe-Glu-Val-Pro-Glu-Val-Thr (3), Trp-Asp-Phe-Val (4), Asn-Met-Trp-Asp-Phe-Val (5) and Gln-Leu-Trp-Pro (6). These peptides, corresponding to CRP sequences 18–19, 48–49 and/or 72–73, 84–90, 162–165, 160–165 and 203–206, respectively, have been synthesized and peptides 2, 3 and in particular peptide 6 were found to significantly inhibit neutrophilic function. The results suggest that CRP-derived peptides may be capable of regulating superoxide ion production by neutrophils in vivo during the acute phase response as part of a complex protective mechanism.     

Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes

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NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal’s behavioral state

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Pathological factors underlying hyperthermia

Hyperthermia is the result of an imbalance between total heat (metabolic heat and environmental heat) accumulated in the body and heat loss from the body, and is defined as a condition when core temperature rises above its normal range. This article will present an overview of syndromes associated with hyperthermia, through discussion of the etiology and pathophysiologic mechanisms that underlie those disorders. Emphasis will also be placed on the therapeutic measures to be taken in order to avert the complications of these disorders.