Hearing loss is the most common sensory deficit in humans with causative variants in over 140 genes. With few exceptions, however, the population-specific distribution for many of the identified ...variants/genes is unclear. Until recently, the extensive genetic and clinical heterogeneity of deafness precluded comprehensive genetic analysis. Here, using a custom capture panel (MiamiOtoGenes), we undertook a targeted sequencing of 180 genes in a multi-ethnic cohort of 342
GJB2
mutation-negative deaf probands from South Africa, Nigeria, Tunisia, Turkey, Iran, India, Guatemala, and the United States (South Florida). We detected causative DNA variants in 25 % of multiplex and 7 % of simplex families. The detection rate varied between 0 and 57 % based on ethnicity, with Guatemala and Iran at the lower and higher end of the spectrum, respectively. We detected causative variants within 27 genes without predominant recurring pathogenic variants. The most commonly implicated genes include
MYO15A
,
SLC26A4
,
USH2A
,
MYO7A
,
MYO6
, and
TRIOBP.
Overall, our study highlights the importance of family history and generation of databases for multiple ethnically discrete populations to improve our ability to detect and accurately interpret genetic variants for pathogenicity.
Hearing loss (HL) is the most common sensory deficit in humans with causative variants in over 140 genes. With few exceptions, however, the population-specific distribution for many of the identified ...variants/genes is unclear. Until recently, the extensive genetic and clinical heterogeneity of deafness precluded comprehensive genetic analysis. Here, using a custom capture panel (MiamiOtoGenes), we undertook a targeted sequencing of 180 genes in a multi-ethnic cohort of 342
GJB2
mutation-negative deaf probands from South Africa, Nigeria, Tunisia, Turkey, Iran, India, Guatemala and the United States (South Florida). We detected causative DNA variants in 25% of multiplex and 7% of simplex families. The detection rate varied between 0% and 57% based on ethnicity, with Guatemala and Iran at the lower and higher end of the spectrum, respectively. We detected causative variants within 27 genes without predominant recurring pathogenic variants. The most commonly implicated genes include
MYO15A, SLC26A4, USH2A, MYO7A, MYO6
and
TRIOBP
. Overall, our study highlights the importance of family history and generation of databases for multiple ethnically discrete populations to improve our ability to detect and accurately interpret genetic variants for pathogenicity.
Mas de 3.000 personas agrupadas en el Frente de Trabajadores Petroleros Desempleados de Caripito tomaron los portones de las instalaciones de Pdvsa en esa poblacion, en protesta por la aplicacion del ...Sistema de Democratizacion de Empleo Petrolero. La accion, dijeron, "es caracter nacional" y por eso hay protestas en todos los lugares petroleros del pais, y se pide la intervencion del Presidente de la Republica, para que solucione el problema. Otro desempleado, Carlos Rojas, quien formo parte del grupo que se traslado hacia las puertas de Miraflores hace 15 dias, para protestar, dijo que tenia ano y medio en la lucha y no habia obtenido una respuesta favorable. "Varias veces nos han indicado que requerimos una carta del presidente Chavez, situacion que nos parece desde todo punto de vista injusta, porque somos militantes del MVR, luchamos para lograr que salieran los golpistas de Pdvsa y resulta que estamos sin empleo' ' . Fin de la protesta Los desempleados que durante una semana mantuvieron una protesta simbolica al acceso al Edificio Sede de Petroleos de Venezuela en Guaraguao, se reunieron ayer con el gerente de Refinacion de Oriente, Fernando Padron, quien antes de incorporarse al encuentro refirio que "no todos los empleos estan en Pdvsa, tenemos el mandato de absorber a las personas que estuvieron en la operacion de contingencia durante el paro petrolero y hay un listado de 46 que esta siendo sometido a analisis".
Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, ...angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy.
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•C-type lectins and TTYH2 are myeloid cell-interacting partners of SARS-CoV-2 spike•C-type lectins interact with spike largely through regions outside of the RBD•Myeloid receptors promote SARS-CoV-2 proinflammatory responses but not infection•A bispecific nanobody blocked SARS-CoV-2 infection and inflammatory responses
Most immune cells express little, if any, of the canonical SARS-CoV-2 receptor, ACE2. Lu et al. report that C-type lectins and TTYH2 act as SARS-CoV-2 myeloid cell-interacting partners that trigger immune hyperactivation but not infection. These findings raise the possibility that these virus-myeloid cell interactions are directly involved in COVID-19 immunopathogenesis and could be targeted for COVID-19 therapy.
The IRAC mapping of the NMBS-II fields program is an imaging survey at 3.6 and 4.5 m with the Spitzer Infrared Array Camera (IRAC). The observations cover three Canada-France-Hawaii Telescope Legacy ...Survey Deep (CFHTLS-D) fields, including one also imaged by AEGIS, and two MUSYC fields. These are then combined with archival data from all previous programs into deep mosaics. The resulting imaging covers a combined area of about 3 deg2, with at least ∼2 hr integration time for each field. In this work, we present our data reduction techniques and document the resulting coverage maps at 3.6 and 4.5 m. All of the images are W-registered to the reference image, which is either the z-band stack image of the 25% best-seeing images from the CFHTLS-D for CFHTLS-D1, CFHTLS-D3, and CFHTLS-D4, or the K-band images obtained at the Blanco 4-m telescope at CTIO for MUSYC1030 and MUSYC1255. We make all images and coverage maps described here publicly available via the Spitzer Science Center.
Problem Mycoplasma genitalium has been associated with male urethritis. We sought to relate M. genitalium to genitourinary signs and symptoms in women.
Method of study We compared 26 ...culture‐positive women (group 1), 257 additional polymerase chain reaction‐positive women (group 2), and 107 negative control women. We used logistic regression to evaluate signs and symptoms, controlling for co‐infections, pregnancy, age, and intervention group assignment.
Results Comparing group 1 with controls, we found significantly elevated odds ratios (ORs) for intermediate vaginal discharge (OR = 5.4; 95% confidence interval 1.01, 29.2) and action in response to discharge 3.9 (1.1, 13.5). Non‐significant increases were observed for pathologic vaginal discharge 3.8 (0.78, 18.2), pathologic dyspareunia 1.5 (0.25, 9.0), vaginal odor 2.1 (0.75, 5.7), and cervical mucopus 4.1 (0.74, 22.4). Group 2 results were similar, but showed no increase in cervical mucopus relative to controls.
Conclusion Infection with M. genitalium in women is independently related to increased genitourinary symptomatology.
Dipyrromethane-2,10-dicarboxylates have been prepared. While oxidation and subsequent reaction of
5b
with BF
3·OEt
2 yields the corresponding complex
10
, ring-closing metathesis of
5d
using ...(NHC)(PCy
3)(Cl)
2RuCHPh
7
results in the novel hybrid macrocycle
8
. The structure of
10
has been unequivocally established by an X-ray crystallographic study.
Dipyrromethane-2,10-dicarboxylates have been prepared and their reactions studied.
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