Skills training, civic engagement and youth forums will help young people become active players in society’s shared efforts to grow and improve.

There’s one big element missing before we can create a truly transparent, seamless and open international trading framework.

Quantum computing could change the face of many international development programs, including those involving transport, financial services and health care.

The over-use of acronyms turns the joy of reading into a tedious process of decoding. It also muddles the message of development communications.

Islamabad : President Arif Alvi on Friday directed that social distancing should be maintained in the upcoming session of the National Assembly for the safety of the parliamentarians and staff against the threat of coronavirus.During a visit to the National Assembly, the president was apprised by...

ISLAMABAD: Chief Justice of the Islamabad High Court (IHC) Justice Athar Minallah on Friday converted the matter relating to delay in administration of justice into public interest litigation and sought reports from the interior secretary, the chief commissioner of Islamabad and judges of trial courts working within the IHC’s jurisdiction.

Chief Justice Minallah asked the police, district administration and federal government to explain why police reforms could not be enforced in the federal capital even though the law had been promulgated some 18 years ago.

The court framed six questions to be answered by these authorities, including why Police Order 2002 could not be implemented in Islamabad; why proper investigation training was not imparted to investigation officers; whether the code of criminal procedure 1898 and Qanoon-i-Shahadat [Evidence Act] of 1984 were still applicable; whether the state was responsible for delay in administration of justice and whether victims of delayed justice could seek remedy from any forum.

The court appointed criminologist Dr Shoaib Suddle, Kamaluddin Tippu, director general of the National Police Bureau, superintendent of Adiala Jail and vice chairmen of the Pakistan Bar Council and Islamabad Bar Council as amici curiae in the matter.

Further hearing was adjourned to May 14.

During the hearing, the inspector general of Islamabad police submitted a report on the problems arising during investigation of crimes which hindered administration of justice.

In the report, the IG said that the investigation officer (IO) of a case had to pay Rs5,000 parcel fee from his own pocket to send evidence to a forensic laboratory for analysis.

“There should not be any laboratory fee or it should be responsibility of the district administration [to pay the fee],” he said.

The IG noted that it took around two months to send evidence to laboratory for analysis. “An IO should be given the authority to send evidence to a laboratory without waiting for the approval of high officials,” he suggested.

Similarly, he said, an IO paid Rs15,000 for preparation of a sketch of a suspect believed to have committed a crime. “Such a sketch should be prepared within two days.”

The report said that plaintiffs did not cooperate with police after registration of first information reports.

The absence of a forensic laboratory in Islamabad, lawyers’ strikes and deployment of police personnel for special duties also delayed investigation process and subsequently trials, the report said.

Earlier, acquitting a murder suspect Chief Justice Minallah had observed that the existing criminal justice system had failed to deliver and it was on the verge of collapse.

The court had observed that the existing criminal justice system failed to prevent and prosecute crime and it was perpetuating miscarriages of justice.

It had noted that low-paid investigating officers did not have sufficient resources to visit the crime scene when a crime was reported, let alone sending the sealed samples and arranging the payment of the fee to a laboratory for conducting forensic examinations.

Published in Dawn, May 9th, 2020

WASHINGTON: The United States on Friday accused China and Russia of stepping up cooperation to spread false narratives over the coronavirus pandemic, saying Beijing was increasingly adopting techniques honed by Moscow.

“Even before the Covid-19 crisis we assessed a certain level of coordination between Russia and the PRC (Peoples Republic of China) in the realm of propaganda,” said Lea Gabrielle, coordinator of the State Department’s Global Engagement Center, which tracks foreign propaganda.

“But with this pandemic the cooperation has accelerated rapidly,” she told reporters.

“We see this convergence as a result of what we consider to be pragmatism between the two actors who want to shape public understanding of the Covid pandemic for their own purposes,” she said.

The Global Engagement Center earlier said that thousands of Russian-linked social media accounts were spreading conspiracies about the pandemic, including charging that the virus first detected last year in the Chinese metropolis of Wuhan was created by the United States.

China outraged the United States when a foreign ministry spokesman tweeted a conspiracy that the US military brought the virus to Wuhan, but the two countries reached an informal rhetorical truce in late March after telephone talks between President Donald Trump and his counterpart Xi Jinping.

Tensions have again soared as Secretary of State Mike Pompeo pushes the theory that the virus originated in a Chinese laboratory, even though both the World Health Organisation and the US government’s top epidemiologist say there is no evidence of this.

According to the Global Engagement Centre, China has again intensified its online campaign to defend its handling of the pandemic, which has killed some 270,000 people worldwide, and criticise the United States.

“Beijing is adapting in real time and increasingly using techniques that have long been employed by Moscow,” Gabrielle said.

China has increasingly used bot networks to amplify its message, Gabrielle said.

She said that official Chinese diplomatic accounts suddenly witnessed a surge in late March, going from adding around 30 new followers daily to more than 720, often from freshly created accounts.

She said that China was first observed using such online methods to “sow political discord” in its autonomous territory of Hong Kong, which has witnessed major pro-democracy demonstrations.

Published in Dawn, May 9th, 2020

NEW DELHI: Is India’s real estate bubble finally bursting? The International Monetary Fund’s recently-launched data series on global housing prices hints at that. Among 52 major markets for which IMF has collated house price data, India has witnessed the steepest fall. IMF’s calculation on the annual percentage change in property prices shows that prices in India fell by 9.1 per cent, the highest among major real estate markets. The fall is even worse than in countries struggling with the ongoing European Union’s financial crisis. Property prices in Greece, Italy, Cyprus, Spain and Portugal have all come down, but at a much slower rate. Ireland, on the other hand, registered a […]

CHENNAI: Strong English speaking skills and a wide mix of industries that promotes cross pollination of work culture has made Chennai one of the top 12 cities in the world for real estate investments. This is the first global recognition the city has received; it is also the lone Indian city on the list. The Candy GPS Report, published on Friday, identifies 12 cities around the globe with the potential to show strong residential property price growth in the next few years. The report — produced by Candy & Candy, Savills World Research and Deutsche Asset & Wealth Management — said, “Prices in these rising cities are generally much lower […]

The government requested financing from the Asian Development Bank (ADB) to support the National Highway Authority (NHA) in constructing new roads and improving existing ones along the backbone from Peshawar to Karachi, to Gwadar Port in Baluchistan, as well as connections between Pakistan and the People’s Republic of China. Following the completion of loan preparatory activities in May 2007 and loan negotiations in October 2007, the ADB Board in December 2007 approved a multitranche financing facility (MFF) for $900 million to support the NTCIP–Tranche 1.

Dentons is now the largest global law firm in Argentina and the first truly Pan-Latin American and the Caribbean firm in the history of the legal profession.

Export performance and firm size have a positive impact on trade participation at the intensive margin for firms of all sizes.

This publication provides estimates of purchasing power parities (PPPs) and real expenditures for 22 economies in Asia and the Pacific. These are summary regional results from the 2017 cycle of the International Comparison Program (ICP).

Export performance and firm size have a positive impact on trade participation at the intensive margin for firms of all sizes.

NEW DELHI: Builders in Noida are unable to hand over more than 30,000 completed homes to their buyers, because of a National Green Tribunal order forbidding the Noida Authority from giving completion certificates to projects within a 10-kilometre radius of the Okhla bird sanctuary. Developers in Noida say they have in the past seven months since the tribunal’s order lost close to Rs 1,000 crore as they have been holding on the flats, paying interest on their loans as well as penalty to home buyers. “Everyone is bleeding,” said Vineet Gupta, director of the Ajnara group, which has around 1,500 apartments waiting to be handed over to buyers. Projects of […]

NEW YORK INTERNATIONAL AUTO SHOW – HARMAN, the premium global audio and infotainment group (NYSE:HAR), is making a strong showing at this year’s New York International Auto Show, with a range of leading automakers featuring HARMAN branded audio systems in vehicles debuting at the show. In addition to the new vehicles– which run the gamut from modern sedans to sports cars, minivans and crossover SUVs – HARMAN technology and solutions can be found in automaker booths throughout the show, a reflection of HARMAN’s longstanding auto partnerships and unmatched industry achievements.

The car is expected to change more in the next five years than it has in the last fifty. What will the future of automotive audio look like? What challenges will suppliers and OEMs alike face in the coming years? At the upcoming International Conference...

With the 2019 National Cybersecurity Awareness Month (NCSAM) upon us, we decided to get the latest download on the state of cybersecurity in the automotive industry from HARMAN’s Vice President & General Manager of Automotive Cybersecurity, Asaf Atzmon....

Stamford, Connecticut – February 03, 2020 – HARMAN International, a wholly-owned subsidiary of Samsung Electronics Co., Ltd. focused on connected technologies for automotive, consumer and enterprise markets, has launched the world’s first active road...

From Northridge, California to Garching, Germany and everywhere in between, HARMAN has been recognizing the achievements and accomplishments of women in recognition of International Women’s Day. Inspired by the campaign’s theme of #BalanceforBetter, the...

In his new book Upheaval, polymath Jared Diamond says nations need a special kind of therapy to solve big problems like climate change, Brexit and nuclear proliferation

Pandemics of the past can teach us about the current one, says John Troyer, who studies how we use technology to alter the experience of death

Elliott vs. Argentina is one of those court cases so important and complex that only a Power Ranger, Transformers, Legos and wooden trains can possibly do it justice. (November 30, 2012)

Georgia's National Ballet, the former Soviet country's famous folk dance ensemble, started giving lessons online after the group's popular dance schools closed their doors due to the coronavirus.

It might be hard to imagine but space is getting crowded. ‘Space junk’ is becoming a dangerous hazard for orbiting satellites, and now some countries are joining forces to tackle it.

In a new report, KPMG ranks countries' autonomous vehicle (AV) readiness by analyzing how policymakers perform on four pillars: policy and legislation, technology and innovation, infrastructure, and consumer acceptance. The top rankings? The...

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ABSTRACT

The cell cycle is a critical component of cellular proliferation, differentiation, and response to stress, yet its role in the regulation of intracellular symbioses is not well understood. To explore host-symbiont cell cycle coordination in a marine symbiosis, we employed a model for coral-dinoflagellate associations: the tropical sea anemone Aiptasia (Exaiptasia pallida) and its native microalgal photosymbionts (Breviolum minutum and Breviolum psygmophilum). Using fluorescent labeling and spatial point-pattern image analyses to characterize cell population distributions in both partners, we developed protocols that are tailored to the three-dimensional cellular landscape of a symbiotic sea anemone tentacle. Introducing cultured symbiont cells to symbiont-free adult hosts increased overall host cell proliferation rates. The acceleration occurred predominantly in the symbiont-containing gastrodermis near clusters of symbionts but was also observed in symbiont-free epidermal tissue layers, indicating that the presence of symbionts contributes to elevated proliferation rates in the entire host during colonization. Symbiont cell cycle progression differed between cultured algae and those residing within hosts; the endosymbiotic state resulted in increased S-phase but decreased G₂/M-phase symbiont populations. These phenotypes and the deceleration of cell cycle progression varied with symbiont identity and host nutritional status. These results demonstrate that host and symbiont cells have substantial and species-specific effects on the proliferation rates of their mutualistic partners. This is the first empirical evidence to support species-specific regulation of the symbiont cell cycle within a single cnidarian-dinoflagellate association; similar regulatory mechanisms likely govern interpartner coordination in other coral-algal symbioses and shape their ecophysiological responses to a changing climate.

IMPORTANCE Biomass regulation is critical to the overall health of cnidarian-dinoflagellate symbioses. Despite the central role of the cell cycle in the growth and proliferation of cnidarian host cells and dinoflagellate symbionts, there are few studies that have examined the potential for host-symbiont coregulation. This study provides evidence for the acceleration of host cell proliferation when in local proximity to clusters of symbionts within cnidarian tentacles. The findings suggest that symbionts augment the cell cycle of not only their enveloping host cells but also neighboring cells in the epidermis and gastrodermis. This provides a possible mechanism for rapid colonization of cnidarian tissues. In addition, the cell cycles of symbionts differed depending on nutritional regime, symbiotic state, and species identity. The responses of cell cycle profiles to these different factors implicate a role for species-specific regulation of symbiont cell cycles within host cnidarian tissues.

ABSTRACT

The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant’s vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor.

IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.

ABSTRACT

Recognition modes of individual T cell receptors (TCRs) are well studied, but factors driving the selection of TCR repertoires from primary through persistent human virus infections are less well understood. Using deep sequencing, we demonstrate a high degree of diversity of Epstein-Barr virus (EBV)-specific clonotypes in acute infectious mononucleosis (AIM). Only 9% of unique clonotypes detected in AIM persisted into convalescence; the majority (91%) of unique clonotypes detected in AIM were not detected in convalescence and were seeming replaced by equally diverse "de novo" clonotypes. The persistent clonotypes had a greater probability of being generated than nonpersistent clonotypes due to convergence recombination of multiple nucleotide sequences to encode the same amino acid sequence, as well as the use of shorter complementarity-determining regions 3 (CDR3s) with fewer nucleotide additions (i.e., sequences closer to germ line). Moreover, the two most immunodominant HLA-A2-restricted EBV epitopes, BRLF1₁₀₉ and BMLF1₂₈₀, show highly distinct antigen-specific public (i.e., shared between individuals) features. In fact, TCRα CDR3 motifs played a dominant role, while TCRβ played a minimal role, in the selection of TCR repertoire to an immunodominant EBV epitope, BRLF1. This contrasts with the majority of previously reported repertoires, which appear to be selected either on TCRβ CDR3 interactions with peptide/major histocompatibility complex (MHC) or in combination with TCRα CDR3. Understanding of how TCR-peptide-MHC complex interactions drive repertoire selection can be used to develop optimal strategies for vaccine design or generation of appropriate adoptive immunotherapies for viral infections in transplant settings or for cancer.

IMPORTANCE Several lines of evidence suggest that TCRα and TCRβ repertoires play a role in disease outcomes and treatment strategies during viral infections in transplant patients and in cancer and autoimmune disease therapy. Our data suggest that it is essential that we understand the basic principles of how to drive optimum repertoires for both TCR chains, α and β. We address this important issue by characterizing the CD8 TCR repertoire to a common persistent human viral infection (EBV), which is controlled by appropriate CD8 T cell responses. The ultimate goal would be to determine if the individuals who are infected asymptomatically develop a different TCR repertoire than those that develop the immunopathology of AIM. Here, we begin by doing an in-depth characterization of both CD8 T cell TCRα and TCRβ repertoires to two immunodominant EBV epitopes over the course of AIM, identifying potential factors that may be driving their selection.

ABSTRACT

The multifunctional nature of viral proteins is essentially driven by posttranslational modifications (PTMs) and is key for the successful outcome of infection. For influenza A viruses (IAVs), a composite pattern of PTMs regulates the activity of viral proteins. However, almost none are known that target the PB2 replication protein, except for inducing its degradation. We show here that PB2 undergoes a nonproteolytic ubiquitination during infection. We identified E3 ubiquitin ligases catalyzing this ubiquitination as two multicomponent RING-E3 ligases based on cullin 4 (CRL4s), which are both contributing to the levels of ubiquitinated forms of PB2 in infected cells. The CRL4 E3 ligase activity is required for the normal progression of the viral cycle and for maximal virion production, indicating that the CRL4s mediate a ubiquitin signaling that promotes infection. The CRL4s are recruiting PB2 through an unconventional bimodal interaction with both the DDB1 adaptor and DCAF substrate receptors. While able to bind to PB2 when engaged in the viral polymerase complex, the CRL4 factors do not alter transcription and replication of the viral segments during infection. CRL4 ligases catalyze different patterns of lysine ubiquitination on PB2. Recombinant viruses mutated in the targeted lysines showed attenuated viral production, suggesting that CRL4-mediated ubiquitination of PB2 contributes to IAV infection. We identified K29-linked ubiquitin chains as main components of the nonproteolytic PB2 ubiquitination mediated by the CRL4s, providing the first example of the role of this atypical ubiquitin linkage in the regulation of a viral infection.

IMPORTANCE Successful infection by influenza A virus, a pathogen of major public health importance, involves fine regulation of the multiple functions of the viral proteins, which often relies on post-translational modifications (PTMs). The PB2 protein of influenza A viruses is essential for viral replication and a key determinant of host range. While PTMs of PB2 inducing its degradation have been identified, here we show that PB2 undergoes a regulating PTM signaling detected during infection, based on an atypical K29-linked ubiquitination and mediated by two multicomponent E3 ubiquitin ligases. Recombinant viruses impaired for CRL4-mediated ubiquitination are attenuated, indicating that ubiquitination of PB2 is necessary for an optimal influenza A virus infection. The CRL4 E3 ligases are required for normal viral cycle progression and for maximal virion production. Consequently, they represent potential candidate host factors for antiviral targets.

APHA member Elena Ong, PHN, MS, past president and founding CEO of the Asian & Pacific Islander Caucus for Public Health, a recent APHA Executive Board member, and a past vice president of the Southern California Public Health Association, discusses discrimination against Asians in the U.S. and beyond.

Medicaid expansion helps pregnant women

Fewer women are dying from pregnancy-related complications in states that have expanded Medicaid, new research finds.

We appreciate the readers' comments on the prevalence and impact of apathy on quality of life among individuals with Parkinson disease. In constructing our survey instrument, we discussed the inclusion of apathy as a symptom. However, we ultimately opted against inclusion because of concerns about the specificity of terminology in our online survey. Patients and care partners may not be familiar with the term "apathy,"and near-synonyms such as "reduced motivation" have substantial overlap with other nonmotor features. Still, as the readers point out, apathy is extremely common and under-recognized. Similar to many of the nonmotor symptoms identified in our study,¹ we agree that clinicians should be screening for apathy among those with Parkinson disease.

We read with great interest the study by Tarolli et al.,¹ which explored the burden of disease in Parkinson disease (PD) by evaluating the prevalence of nonmotor symptoms and their association with quality of life. The authors selected nonmotor symptoms based on literature review, expert opinions, and patient interviews. We note that apathy, which has major consequences for patients and carers, was not included as a relevant nonmotor symptom in their study. We performed a subcohort analysis of 60 patients from a study of pain in PD in 110 outpatients (PaCoMo-study, registered trial number: NL6311402917 [toetsingonline.nl]). We retrospectively reviewed the medical records to check whether the clinician identified apathy in these patients in the previous year, which was the case in 15% of the patients (n = 9). Blind to those results, patients were examined with the Apathy Scale (AS).² In total, 63.3% (n = 38) of the patients scored positive on the AS. Only 18.4% of the patients who scored positive on the AS were also classified or mentioned with apathy in the medical records by clinicians.

BACKGROUND:

Although autodialer centralized reminder and recall (C-R/R) from state immunization information systems (IISs) has been shown to raise childhood vaccination rates, its impact on human papillomavirus (HPV) vaccination rates is unclear.

OBJECTIVES:

Standing orders are an effective way to increase vaccination rates, yet little is known about how pediatricians use this strategy for childhood immunizations. We assessed current use of, barriers to using, and factors associated with use of standing orders for vaccination among pediatricians.

Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine. CD8 T cell responses recognized epitopes from multiple flaviviruses; however, the magnitude of cross-reactive responses was consistently severalfold lower than those to the autologous epitope pools and was associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing 29 different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with >100-fold-lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV-derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses and in five out of eight cases >1,000-fold-lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and have implications for understanding immunity elicited by natural infection and strategies to develop live attenuated vaccines against flaviviral species.

IMPORTANCE The envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the nonstructural (NS) and capsid (C) antigens, which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses among different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses and might thus impair vaccine performance.