The tuberal hypothalamus is comprised of the dorsomedial, ventromedial, and arcuate nuclei, as well as parts of the lateral hypothalamic area, and it governs a wide range of physiologies. During neurogenesis, tuberal hypothalamic neurons are thought to be born in a dorsal-to-ventral and outside-in pattern, although the accuracy of this description has been questioned over the years. Moreover, the intrinsic factors that control the timing of neurogenesis in this region are poorly characterized. Proneural genes, including Achate-scute-like 1 (Ascl1) and Neurogenin 3 (Neurog3) are widely expressed in hypothalamic progenitors and contribute to lineage commitment and subtype-specific neuronal identifies, but the potential role of Neurogenin 2 (Neurog2) remains unexplored. Birthdating in male and female mice showed that tuberal hypothalamic neurogenesis begins as early as E9.5 in the lateral hypothalamic and arcuate and rapidly expands to dorsomedial and ventromedial neurons by E10.5, peaking throughout the region by E11.5. We confirmed an outside-in trend, except for neurons born at E9.5, and uncovered a rostrocaudal progression but did not confirm a dorsal-ventral patterning to tuberal hypothalamic neuronal birth. In the absence of Neurog2, neurogenesis stalls, with a significant reduction in early-born BrdU⁺ cells but no change at later time points. Further, the loss of Ascl1 yielded a similar delay in neuronal birth, suggesting that Ascl1 cannot rescue the loss of Neurog2 and that these proneural genes act independently in the tuberal hypothalamus. Together, our findings show that Neurog2 functions as a classical proneural gene to regulate the temporal progression of tuberal hypothalamic neurogenesis.

SIGNIFICANCE STATEMENT Here, we investigated the general timing and pattern of neurogenesis within the tuberal hypothalamus. Our results confirmed an outside-in trend of neurogenesis and uncovered a rostrocaudal progression. We also showed that Neurog2 acts as a classical proneural gene and is responsible for regulating the birth of early-born neurons within the ventromedial hypothalamus, acting independently of Ascl1. In addition, we revealed a role for Neurog2 in cell fate specification and differentiation of ventromedial -specific neurons. Last, Neurog2 does not have cross-inhibitory effects on Neurog1, Neurog3, and Ascl1. These findings are the first to reveal a role for Neurog2 in hypothalamic development.

Elvis Cortés Hernández grabs his lunch and sits down with his friends. We’re at the General Lázaro Cárdenas school in Ajalpan, deep in the heart of Mexico’s Puebla province and the ten–year–old is chatting about the school’s vegetable garden, one element of its progressive food policy. “I like to eat in the school dining room because they give me carrots, [...]

1. ‘Army won’t be deployed in Mumbai, will fight Covid-19 together’: Uddhav Thackeray  Hindustan Times
2. Maharashtra may extend lockdown to end of May, hints CM Uddhav Thackeray  Times of India
3. Maharashtra CM Uddhav Thackeray announces compensation for kin of deceased  TIMES NOW
4. Restrict entry-exit of migrants in Maharashtra: Raj Thackeray  Deccan Chronicle
5. Uddhav Thackeray: You are the soldiers, no need for the Army  Mumbai Mirror
6. View Full coverage on Google News

OM Hungary works alongside partner organisations to bring comfort and Jesus’ love to refugees in Budapest.

Fourteen young people participated in a month-long outreach within in their country. The result: unity.

OM Hungary works alongside partner organisations to bring comfort and Jesus’ love to refugees in Budapest.

Softball ministry in Hungary shows hospitality, international influence by hosting the 2016 Danube Cup

CNA Staff, May 5, 2020 / 10:00 am (CNA).- Poland’s bishops have intervened in a debate about whether presidential elections scheduled for May 10 should go ahead despite a nationwide lockdown.

A statement from the permanent council of the Polish bishops’ conference April 27 urged politicians to work together to ensure that the election would be regarded as legitimate by all sides. 

It said: “We appeal to the consciences of those responsible for the common good of our homeland, both those in power and the opposition, to work out a common position on the presidential elections in this extraordinary situation.” 

Poland’s ruling coalition, led by the Law and Justice (PiS) party, has rejected calls to postpone the election, due to take place this Sunday. 

The state began introducing lockdown measures March 10, which it is now starting to lift. Poland, which has a population of almost 38 million, had 14,242 documented coronavirus cases and 700 deaths as of May 5, according to Johns Hopkins University Coronavirus Resource Center.

The Polish Senate began debating legislation May 5 that would allow the election to be held by postal vote, rather than at polling stations, due to the pandemic. 

The Sejm, the lower chamber of the Polish parliament, will have the final say on the legislation. 

The bishops called on lawmakers to resolve the issue while upholding the principles of Poland’s constitution. They emphasized that they were not seeking to engage in “purely political disputes over the form or timing of election, let alone to advocate this or that solution.”

The bishops’ permanent council said: “We encourage dialogue between the parties to seek solutions that would not raise legal doubts and suspicion, not only of a violation of the current constitutional order but also of the principles of free and fair elections adopted in a democratic society.”

“We ask that, guided by the best will, they would seek in their actions the common good, which today is expressed both by the life, health and social existence of Poles, as well as broad social trust in the electoral procedures of a democratic state jointly developed over the years.”

The bishops continued: “In this difficult situation that we are experiencing, we should take care to cultivate a mature democracy, protect the nation of laws, building -- despite differences -- a culture of solidarity, also in the political sphere.”

If parliament approves the postal vote, the government could delay the vote to either May 17 or May 23 to allow more preparation time, according to Reuters. 

Opinion polls suggest the incumbent President Andrzej Duda, a PiS ally, would be re-elected by a significant margin if the vote were held soon. 

Bishops’ conference president Archbishop Stanisław Gądecki entrusted Poland to the Most Sacred Heart of Jesus and to Our Lady, Queen of Poland, at Jasna Góra Monastery in Częstochowa May 3.

OM Hong Kong celebrates the annual Mid-Autumn Festival with South Asian friend and meets other families to learn about their needs.

OBJECTIVES:

Reduce postoperative hypothermia by up to 50% over a 12-month period in children’s hospital NICUs and identify specific clinical practices that impact success.

Various OM ministries partner with the Irish Evangelistic Band to share the good news at Ireland's National Ploughing Championship.

AN EDINBURGH-BASED hydrogen technology firm is to open the first public hydrogen refuelling station for vehicles in Scotland’s central belt.

A SCOTTISH clean energy company has secured a key part in a six-figure contract for a hydrogen fuel project in Northern Ireland.

Russia's Teenagers Football League, the springboard to success for Yuri Zhirkov and Alan Dzagoev, has held a series of events aimed at uniting different faiths and nationalities.

Food insecurity has been linked to childhood obesity in a number of studies. Few studies have explored potential pathways through which food insecurity is related to child weight, especially in low-income families with young infants.

We found that food insecurity was related to maternal controlling feeding styles and concerns about the infants’ future weight. Early obesity prevention should aim to decrease food insecurity and to reduce controlling feeding styles in families who remain food insecure. (Read the full article)

Neonatal sepsis is an important cause of under-5 childhood mortality. Infants born to HIV-infected mothers are at increased risk of morbidity and mortality, even if not having acquired HIV. This association needs further study during the neonatal period.

Maternal HIV infection was associated with increased vaginal colonization by Escherichia ecoli but not group B Streptococcus. Neonates born to HIV-infected mothers were only at increased risk of sepsis if they had acquired HIV-infection, but not if HIV-uninfected. (Read the full article)

Childhood obesity occurs in 20% of children before they enter kindergarten. Treatment is difficult, making prevention desirable, but little is known about effective methods using anticipatory guidance to prevent obesity in pediatric primary care.

This study provides a comparison of 2 approaches versus usual care using anticipatory guidance to improve infant feeding during the first year of life, and demonstrates positive specific feeding behavior differences at 1 year in the intervention groups. (Read the full article)

Adult patients with neurocardiogenic syncope have shown high rates of depression. Patients with more severe depressive symptoms have higher rates of syncope recurrence. Psychiatric interventions improve quality of life and decrease syncope recurrence rates.

Children with neurocargiogenic syncope presented a 2.6-fold higher rate of clinically significant depressive symptoms compared to healthy controls. No recurrent syncope was noted during follow-up which along with improvement in family functioning predicted depressive symptoms improvement. (Read the full article)

Anabolic-androgenic steroid misuse is not uncommon among adolescent boys, and initial use in adolescence is associated with a host of maladaptive outcomes, including cardiovascular, endocrine, and psychiatric complications.

This is the first known study to examine prevalence rates of anabolic-androgenic steroid misuse as a function of sexual orientation. A dramatic disparity was found, in that sexual minority boys reported misuse at a much higher rate than heterosexual boys. (Read the full article)

As technical improvements of pharmacogenetics (PGx) continue to be made, little is known about the perceptions of the public, in particular parents and children, on the topic of PGx.

If PGx testing is for oneself, differences in opinion are due to baseline PGx knowledge, regardless of whether respondents are parents or not. If PGx testing is for children, parents would prioritize their own understanding above their child’s assent. (Read the full article)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an important risk factor for neonatal jaundice in Nigeria. It is associated with severe hyperbilirubinemia among infants exposed to icterogenic agents. Elevated bilirubin levels have occasionally been demonstrated in G6PD-deficient infants without exposure to icterogenic agents.

Even without exposure to known icterogens, G6PD-deficient infants have a more rapid hematocrit decline and higher bilirubin levels than their G6PD-intermediate and G6PD-normal counterparts throughout the first week of life. (Read the full article)

Asthma is heterogeneous and 40% to 70% of patients fail to achieve control with current treatment strategies. To delineate relevant subphenotypes of asthma, identify key factors, and test novel interventions, comprehensive repositories linking clinical, environmental, and biologic data are required.

This is the first statewide repository for inpatient pediatric asthma. The data collected will better define asthma phenotypes, identify care practices associated with the best health outcomes, and inform personalized care plans to reduce reutilization and readmission for pediatric asthma. (Read the full article)

Clinical trials of the quadrivalent human papillomavirus vaccine show it to be highly efficacious in preventing vaccine-type–specific cervical dysplasia and anogenital warts, but few studies have assessed its effects in the real world and none have done so at the program/population level.

This study provides strong evidence of the early benefits of quadrivalent human papillomavirus vaccination on reductions in cervical dysplasia and possible reductions in anogenital warts among girls aged 14 to 17 years, offering additional justification for not delaying vaccination until girls are older. (Read the full article)

Prophylactic vaccination of young women 16 to 26 years of age with the 9-valent human papillomavirus (HPV)–like particle (9vHPV) vaccine prevents infection and disease with vaccine HPV types.

These data support bridging the efficacy findings with 9vHPV vaccine in young women 16 to 26 years of age to girls and boys 9 to 15 years of age and implementation of gender-neutral HPV vaccination programs in preadolescents and adolescents. (Read the full article)

The routine childhood immunization schedule is crowded during the first 2 years, leading to deferred doses and limiting the addition of new vaccines. Combination vaccines can reduce the "shot burden" and improve coverage rates and timeliness.

Antibody response rates to antigens contained in an investigational hexavalent vaccine (DTaP5-IPV-Hib-HepB) were noninferior to licensed comparator vaccines when given as a 3-dose infant series. The safety profile was similar to control except for increased rates of mild-to-moderate, self-limited fever. (Read the full article)

Glucose-6-phosphate dehydrogenase deficiency remains a global as well as a North American burden for extreme hyperbilirubinemia and kernicterus and is often unpredictable during the first few days after birth. Newborn screening for this enzyme deficiency is not universally available but debated.

Point-of-care screening, using digital microfluidics, provides accurate, low blood volume, and affordable technology for rapid newborn glucose-6-phosphate dehydrogenase enzyme screening that could guide clinicians before infants’ discharge from well-child nurseries and meet existing American Academy of Pediatrics’ recommendations. (Read the full article)

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo β-lactamase (MBL) families. The recent introduction of SBL carbapenemase-inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n=234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ~30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modelling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor, capable of operating in a functional space not presently filled by any clinically approved compound.

Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, an early step in the conserved glycosylphosphotidyl inositol (GPI) post-translational modification pathway of surface proteins in eukaryotic cells. Inhibition of inositol acylation by MGX results in pleiotropic effects including inhibition of maturation of GPI-anchored proteins necessary for growth and virulence. MGX has been previously shown to have in vitro activity against some strains of Mucorales. Here we assessed the in vivo activity of the prodrug fosmanogepix, currently in clinical development for the treatment of invasive fungal infections, against two Rhizopus arrhizus strains with high (4.0 μg/ml) and low (0.25 μg/ml) minimum effective concentration (MEC) values. In both invasive pulmonary infection models, treatment of mice with 78 mg/kg or 104 mg/kg fosmanogepix, along with 1-aminobenzotriazole to enhance the serum half-live of MGX in mice, significantly increased median survival time and prolonged overall survival by day 21 post infection when compared to placebo. In addition, administration of fosmanogepix resulted in a 1-2 log reduction in both lung and kidney fungal burden. For the 104 mg/kg fosmanogepix dose, tissue clearance and survival were comparable to clinically relevant doses of isavuconazole (ISA), which is FDA approved for the treatment of mucormycosis. These results support continued development of fosmanogepix as a first in class treatment for invasive mucormycosis.

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases observed in biochemical assays. Microbiological studies using characterized strains were used to provide a comprehensive characterization of the spectrum of beta-lactamase inhibition by QPX7728. The MIC of multiple IV only (ceftazidime, piperacillin, cefepime, ceftolozane and meropenem) and orally bioavailable (ceftibuten, cefpodoxime, tebipenem) antibiotics alone and in combination with QPX7728 (4 μg/ml), as well as comparator agents, were determined against the panels of laboratory strains of P. aeruginosa and K. pneumoniae expressing over 55 diverse serine and metallo beta-lactamases. QPX7728 significantly enhanced the potency of antibiotics against the strains expressing Class A extended spectrum beta-lactamases (CTX-M, SHV, TEM, VEB, PER) and carbapenemases (KPC, SME, NMC-A, BKC-1), consistent with beta-lactamase inhibition demonstrated in biochemical assays. It also inhibits both plasmidic (CMY, FOX, MIR, DHA) and chromosomally encoded (P99, PDC, ADC) Class C beta-lactamases and Class D enzymes including carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from Acinetobacter baumannii (OXA-23/24/72/58). QPX7728 is also a potent inhibitor of many class B metallo beta-lactamases (NDM, VIM, CcrA1, IMP, GIM but not SPM or L1). Addition of QPX7728 (4 μg/ml) reduced the MICs in a majority of strains to the level observed for the vector alone control, indicative of complete beta-lactamase inhibition. The ultra-broad-spectrum beta-lactamase inhibition profile makes QPX7728 a viable candidate for further development.

In vitro and in vivo interactions of minocycline and azoles including itraconazole, voriconazole, and posaconazole against filamentous pathogenic fungi were investigated. A total of 56 clinical isolates were studied in vitro via broth microdilution checkerboard technique, including 20 strains of Aspergillus fumigatus, 7 strains of A. flavus, 16 strains of Exophiala dermatitidis, 10 strains of Fusarium solani and 3 strain s of F. oxysporum. The results revealed that minocycline individually did not exhibit any significant antifungal activity against all tested strains. However, favorable synergy of minocycline with itraconazole, voriconazole, or posaconazole were observed against 34 (61%), 28 (50%), and 38 (69%) isolates, respectively, including azole resistant A. fumigatus and Fusarium spp. with inherently high MICs of azoles. Synergistic combinations resulted in 4 fold to 16-fold reduction of effective MICs of minocycline and azoles. No antagonism was observed. In vivo effect of minocycline-azole combinations were evaluated by survival assay in Galleria mellonella model infected with E. dermatitidis strain BMU00034, F. solani strain FS9, A. fumigatus strain AF293, AFR1 and AFR2 . Minocycline acted synergistically with azoles and significantly increased larvae survival in all isolates (P<0.001), including azole resistant A. fumigatus and azole-inactive Fusarium spp.. In conclusion, the results suggested that minocycline combined with azoles may help to enhance the antifungal susceptibilities of azoles against pathogenic fungi and had the potential to overcome azole resistance issues.

Attention has been paid to H5N6 highly pathogenic avian influenza virus (HPAIV) because of its heavy burden on the poultry industry and human mortality. Since an influenza A virus carrying N6 neuraminidase (NA) has never spread in humans, the potential for H5N6 HPAIV to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. We used non-human primates to elucidate the pathogenesis of H5N6 HPAIV as well as to determine the efficacy of antiviral drugs against the virus. H5N6 HPAIV infection led to high fever in cynomolgus macaques. The lung injury caused by the virus was severe with diffuse alveolar damage and neutrophil infiltration. In addition, an increase in IFN-α showed an inverse correlation with virus titers during the infection process. Oseltamivir was effective for reducing H5N6 HPAIV propagation, and continuous treatment with peramivir reduced virus propagation and severity of symptoms in the early stage. This study also showed the pathologically severe lung injury states in the cynomolgus macaques infected with H5N6 HPAIV, even in those that received early antiviral drug treatments, indicating the need for close monitoring and the need for further studies on the virus pathogenicity and new antiviral therapies.

Manogepix (APX001A) is the active moiety of the novel drug candidate fosmanogepix (APX001). We previously reported the broad-spectrum activity of manogepix but also observed a correlation between increased manogepix and fluconazole MICs. Here we extended this study and included isolates with acquired fluconazole resistance.

Isolates (n=835) were identified using CHROMagar, MALDI-TOF and, when needed, ITS-sequencing. EUCAST E.Def 7.3.1 susceptibility testing included manogepix, amphotericin B, anidulafungin, micafungin, fluconazole and voriconazole. Manogepix wildtype-upper-limit (WT-UL) values were established following EUCAST-principles for ECOFF setting allowing wildtype/non-wildtype classification. Drug-specific MIC correlations were investigated using Pearson's correlation.

Manogepix modal MICs were low (range 0.004-0.06 mg/L against 16/20 included species). Exceptions were C. krusei and C. inconspicua, and to a lesser extent C. kefyr and Pichia kluyveri. The activity was independent of Fks echinocandin hot-spot alterations (n=17). Adopting the WT-UL established for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and C. tropicalis, 14/724 (1.9%) isolates were non-wildtype for manogepix. Twelve of these (85.7%) were also non-wildtype for fluconazole. A statistically significant correlation was observed between manogepix and fluconazole MICs for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and C. tropicalis (Pearson r=0.401-0.575), but not between manogepix and micafungin or amphotericin B MICs for any species except C. tropicalis (r=0.519 for manogepix versus micafungin).

Broad-spectrum activity was confirmed for manogepix against contemporary yeast. However, a 1-4 two-fold-dilution increase in manogepix MICs is observed in a subset of isolates with acquired fluconazole resistance. Further studies on the potential underlying mechanism and implication for optimal dosing are warranted.

I was just sitting down to write this week's column when the Red Arrows flew right over my head.

The staff of Hershey Medical Center is one of only several academic hospitals in the country with specialized infrastructure and and training geared around offering care during a contagion outbreak. But they have another advantage, too. “We are all a family,” says one doctor. “And we look out for one another.”

The UK and Scottish Governments must work more closely together to ensure people get the benefits they are entitled to, a new report by the Scottish Parliament’s Social Security Committee has said.

Europe's most famous footballing families are supporting a new TV campaign by UEFA which calls on dads to encourage their daughters to play football.

Riverboat community members took to the city centre for an afternoon and–to their surprise–met people who spoke their heart languages.

By manipulating the expression of one gene, geneticists can induce a form of “stress memory” in plants that is inherited by some progeny, giving them the potential for more vigorous, hardy and productive growth, according to Penn State researchers, who suggest the discovery has significant implications for plant breeding.

Citizen coders and civic technologists from across Delaware are set to take on the state’s second annual Open Data Challenge, harnessing the power of public datasets to come up with new solutions to big statewide problems.

The US Department of Commerce is close to signing off on a new rule that would allow US companies to work with China's Huawei Technologies on setting standards for next generation 5G networks, people...

With the passing of former State Senator Roger Martin on Thursday, October 27 Governor Carney has ordered the United States and Delaware flags at state buildings and facilities be flown at half-staff beginning Friday morning, November 3 as a mark of respect for Mr. Martin and his service to Delaware. Mr. Martin was elected to […]

NEW CASTLE (Sept. 25, 2019) – Department of Health and Social Services employees joined together with the Food Bank of Delaware, legislators and other volunteers to distribute 30,000 pounds of non-perishable food, fresh produce and dairy products to Delawareans in need during a drive-through event today at DHSS’ Herman Holloway Campus near New Castle. The […]

India is among the last set of nations to face the Covid-19 outbreak, but the longer it takes to shape its economic response, the costlier its interventions will be, according to industry executives.

Encouraging data sharing can sometimes feel like refereeing kids on Christmas morning. “Mom said you have to SHARE!” my sister bawled, grabbing at the Game Boy in my hand as I held the toy just out of her reach. I had just gotten it as a Christmas present and had [...]

The post With government data sharing, don’t be a data scrooge appeared first on Government Data Connection.

With US President Donald Trump preparing to square off with presumptive Democratic nominee Joe Biden in the 2020 race, Americans might as well be choosing between Orwell and Huxley, Pink Floyd co-founder Roger Waters told RT.
Read Full Article at RT.com

Effects observed in male rats

Jaiprakash Dandegaonkar, ex-minister of state for co-operation, Maharashtra has been elected as the vice president of the association.

https://community.cadence.com/cadence_blogs_8/b/breakfast-bytes/posts/cowos-info

I came across cadence old article that discussing about TSMC advance packaging technology such as InFO & CoWoS. However, I couldn’t find information such as what I/O interface standard is required to realize this multi-chip SiP. For example, Intel using their proprietary AIB interface for EMIB solution.

Besides, any idea if inFO also able to supports multi-chip integration for older node process to new node process such as 40-nm to 16-nm?