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Ian Iqbal Rashid

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129-614: Ian Iqbal Rashid (born in Dar es Salaam , Tanzania ) is a poet, screenwriter and filmmaker known in particular for his volumes of poetry, for the TV series Sort Of and This Life and the feature films Touch of Pink and How She Move . Of Indian ancestry and raised in the Ismaili Muslim faith, Rashid's family lived in colonial East Africa for generations. Different years of birth are given for Rashid in different sources, but academic work gives

258-490: A long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell. The Psi element is involved in viral genome packaging and recognized by gag and rev proteins. The SLIP element ( TTTTTT ) is involved in the frameshift in the gag - pol reading frame required to make functional pol . The term viral tropism refers to

387-706: A Mayor." According to Associational Life in African Cities: Popular Responses to the Urban Crisis , published in 2001: "Until June 1996, Dar es Salaam was managed by the Dar es Salaam City Council...the highest policy-making body in the city." As of 2017, Paul Makonda serves as the commissioner of Dar es Salaam Region. Dar es Salaam is the most populous city in Tanzania and the fifth most populous in Africa. In 2020,

516-496: A beachfront suburb on a peninsula, is home to an economically diverse population. Access to the suburb is mainly by ferry, although the Kigamboni Bridge provides an alternative. Dar es Salaam experiences tropical climatic conditions, typified by hot and humid weather throughout much of the year due to its proximity to the equator and the warm Indian Ocean. It has a tropical savanna climate ( Köppen : Aw / As ). Annual rainfall

645-521: A bidding war, and eventually, a sale to Sony Picture Classics . The film has attracted extensive scholarly commentary. in 2024, Sanghum Film Collective hosted a 20th-anniversary screening and celebration of the film at the legendary Paradise Theatre in Toronto. How She Move received a similarly positive reception at the Sundance Film Festival . Directed by Rashid in 2007, the film is set in

774-535: A cell by a virion can be called "cell-free spread" to distinguish it from a more recently recognized process called "cell-to-cell spread". In cell-free spread (see figure), virus particles bud from an infected T cell, enter the blood or extracellular fluid and then infect another T cell following a chance encounter. HIV can also disseminate by direct transmission from one cell to another by a process of cell-to-cell spread, for which two pathways have been described. Firstly, an infected T cell can transmit virus directly to

903-481: A cell surface. The unusual processing and high density means that almost all broadly neutralising antibodies that have so far been identified (from a subset of patients that have been infected for many months to years) bind to, or are adapted to cope with, these envelope glycans. The molecular structure of the viral spike has now been determined by X-ray crystallography and cryogenic electron microscopy . These advances in structural biology were made possible due to

1032-414: A few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection. Modern HIV testing is extremely accurate, when the window period is taken into consideration. A single screening test is correct more than 99% of the time. The chance of a false-positive result in a standard two-step testing protocol

1161-494: A fourth collection is rumoured. His poems have appeared in journals and been anthologized widely including the poems "Another Country", "Could Have Danced All Night", "Hot Property" and "Early Dinner, Weekend Away" in John Barton and Billeh Nickerson 's 2007 anthology Seminal: The Anthology of Canada's Gay Male Poets ,. More early work is included in the 2009 anthology Forbidden Sex, Forbidden Texts: New India's Gay Poets . He

1290-448: A human host cell when the newly formed virus particle buds from the cell. The viral envelope contains proteins from the host cell and relatively few copies of the HIV envelope protein, which consists of a cap made of three molecules known as glycoprotein (gp) 120 , and a stem consisting of three gp41 molecules that anchor the structure into the viral envelope. The envelope protein, encoded by

1419-568: A key step in the progression to AIDS. A number of studies with subtype B-infected individuals have determined that between 40 and 50 percent of AIDS patients can harbour viruses of the SI and, it is presumed, the X4 phenotypes. HIV-2 is much less pathogenic than HIV-1 and is restricted in its worldwide distribution to West Africa . The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of co-receptor usage (including CD4-independence) may assist

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1548-416: A long and healthy life at film festivals. Rashid went on to write two award-winning short films, Surviving Sabu (1999, Arts Council of England) and Stag (2001, BBC Films ). Touch of Pink , Rashid's first feature film, spent 12 years in development. In 2003, he finally had the chance to direct the project as a Canada-UK co-production. It premiered at the 2004 Sundance Film Festival to great acclaim,

1677-466: A metro bus system, Dar es Salaam bus rapid transit ( mwendo kasi in Kiswahili). The metro buses are managed by UDA-RT, a partnership between Usafiri Dar es Salaam (UDA) and the government. The bus rapid-transit system Phase 1 has been completed by UDA-RT and began operation on 10 May 2016. The first section runs between Kimara in the northwest to Kivukoni on the northern headland of the harbour. Phase 1

1806-555: A more centrally located city in the interior. The relocation process to Dodoma was completed, although Dar es Salaam continued to be the location of most government offices. In 1967, the Tanzanian government declared the ujamaa policy, which made Tanzania lean towards socialism . The move hampered the potential growth of the city as the government encouraged people not to move into cities and instead remain in Ujamaa socialist villages. By

1935-600: A more stable conformation following the NC binding, in which both the DIS and the U5:AUG regions of the gRNA participate in extensive base pairing. RNA can also be processed to produce mature messenger RNAs (mRNAs). In most cases, this processing involves RNA splicing to produce mRNAs that are shorter than the full-length genome. Which part of the RNA is removed during RNA splicing determines which of

2064-447: A number of mechanisms, including pyroptosis of abortively infected T cells, apoptosis of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4 T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4 T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to

2193-585: A period of rapid growth. Political developments, including the formation and growth of the Tanganyika African National Union , led to Tanganyika's independence from colonial rule in December 1961. Dar es Salaam continued to serve as its capital, even when Tanganyika and the People's Republic of Zanzibar merged to form Tanzania in 1964. In 1973, provisions were made to relocate the capital to Dodoma ,

2322-753: A quarterly journal covering South Asian arts in the UK in the early 1990s. Ian's personal essays have also been published in Wasafiri , Third Text and The Globe and Mail . Rashid has also curated film programmes and exhibitions for venues such as the National Film Theatre , the Institute of Contemporary Arts and Experimenta . He was the founder and first director of Desh Pardesh , Canada's first arts festival focusing on diasporic South Asian arts and culture. Amongst many awards and festival prizes, Rashid has received

2451-411: A strain of SIV found in sooty mangabees. Since HIV-1 is derived from SIVcpz, and HIV-2 from SIVsm, the genetic sequence of HIV-2 is only partially homologous to HIV-1 and more closely resembles that of SIVsm. Many HIV-positive people are unaware that they are infected with the virus. For example, in 2001 less than 1% of the sexually active urban population in Africa had been tested, and this proportion

2580-558: A target T cell via a virological synapse . Secondly, an antigen-presenting cell (APC), such as a macrophage or dendritic cell, can transmit HIV to T cells by a process that either involves productive infection (in the case of macrophages) or capture and transfer of virions in trans (in the case of dendritic cells). Whichever pathway is used, infection by cell-to-cell transfer is reported to be much more efficient than cell-free virus spread. A number of factors contribute to this increased efficiency, including polarised virus budding towards

2709-451: A transportation link to most large Dar es Salaam urban nodes. The narrow-gauge commuter rail runs from there to the city centre, with ten level crossings along the route. This district is characterised with a lot of potential social and economic centres such as industries i.e. Urafiki textile industry, bus station and various institutes and universities such as National Institute of Transport(NIT) Kigamboni (also known as South Beach),

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2838-424: Is a Hindu temple like Shree Shankarashram temple, Shree Sanatan Dharma Sabha temple, Swaminarayan temple. Muslims make up 70% of the population in Dar es Salaam. HIV The human immunodeficiency viruses ( HIV ) are two species of Lentivirus (a subgroup of retrovirus ) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of

2967-502: Is a cultural centre, workshop and retail outlet dedicated to Tanzanian art, showcasing and promoting Tanzanian craftsmanship. Prominent Tanzanian sculptor George Lilanga has donated some of his works to the centre, including decorations of the building's main entrance. The music scene in Dar es Salaam is divided among several styles. The longest-standing style is live dance music ( muziki wa dansi ) played by bands such as DDC Mlimani Park Orchestra and Malaika Musical Band. Taarab , which

3096-536: Is a new railway station currently under construction. It will link the country to Rwanda, Uganda, Burundi and Congo. The Julius Nyerere International Airport is the principal airport serving the country, with three operating terminals. Terminal Three is located at Kipawa in Ilala Municipality. The airport is located west of Dar es Salaam's central business district. The Tingatinga painting style originates from Dar es Salaam. The Nyumba ya sanaa ("House of Art")

3225-456: Is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit. The final step of the viral cycle, assembly of new HIV-1 virions, begins at the plasma membrane of the host cell. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi apparatus where it is cleaved by furin resulting in

3354-579: Is approximately 1,150 millimetres or 45 inches, and in a normal year there are two rainy seasons: the "long rains" in April and May, and the "short rains" in November and December. A 2019 paper published in PLOS One estimated that under Representative Concentration Pathway 4.5 , a "moderate" scenario of climate change where global warming reaches ~2.5–3 °C (4.5–5.4 °F) by 2100, the climate of Dar es Salaam in

3483-507: Is bound with the CD4 protein, the envelope complex undergoes a structural change, exposing the chemokine receptor binding domains of gp120 and allowing them to interact with the target chemokine receptor. This allows for a more stable two-pronged attachment, which allows the N-terminal fusion peptide gp41 to penetrate the cell membrane. Repeat sequences in gp41, HR1, and HR2 then interact, causing

3612-484: Is commonly translated from Arabic as "abode (home) of peace", from dar ("house"), and es salaam ("of peace"). Dar es Salaam fell into decline after Majid's death in 1870, but was revived in 1887 when the German East Africa Company established a station there. The town's growth was facilitated by its role as the administrative and commercial centre of German East Africa and industrial expansion following

3741-424: Is even lower in rural populations. Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or received their test results. Again, this proportion is even lower in rural health facilities. Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV. HIV-1 testing

3870-464: Is high as the glycans shield the underlying viral protein from neutralisation by antibodies. This is one of the most densely glycosylated molecules known and the density is sufficiently high to prevent the normal maturation process of glycans during biogenesis in the endoplasmic and Golgi apparatus. The majority of the glycans are therefore stalled as immature 'high-mannose' glycans not normally present on human glycoproteins that are secreted or present on

3999-399: Is initially done using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a non-reactive result from the initial ELISA are considered HIV-negative, unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate. If the result of either duplicate test is reactive,

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4128-447: Is largely confined to West Africa . HIV is similar in structure to other retroviruses. It is roughly spherical with a diameter of about 120  nm , around 100,000 times smaller in volume than a red blood cell . It is composed of two copies of positive- sense single-stranded RNA that codes for the virus' nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein p24 . The single-stranded RNA

4257-601: Is more likely, leading to immunodeficiency. Three groups of HIV-1 have been identified on the basis of differences in the envelope ( env ) region: M, N, and O. Group M is the most prevalent and is subdivided into eight subtypes (or clades ), based on the whole genome, which are geographically distinct. The most prevalent are subtypes B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes form branches in

4386-555: Is present as both free virus particles and virus within infected immune cells . Research has shown (for both same-sex and opposite-sex couples) that HIV is not contagious during sexual intercourse without a condom if the HIV-positive partner has a consistently undetectable viral load . HIV infects vital cells in the human immune system, such as helper T cells (specifically CD4 T cells), macrophages , and dendritic cells . HIV infection leads to low levels of CD4 T cells through

4515-464: Is referenced in the Oxford Companion to Canadian Literature and Making a Difference:Canadian Multicultural Literature . He wrote and read his short story "Muscular Bridges" for BBC Radio 4 's 50th HMT Windrush Anniversary, which later evolved into the feature film Touch of Pink Rashid has also written song lyrics, most notably for his film Touch of Pink . In the late 1980s, Rashid

4644-580: Is the largest city and financial hub of Tanzania . It is also the capital of the Dar es Salaam Region . With a population of over nine million people, Dar es Salaam is the largest city in East Africa by population and the sixth-largest in Africa . Located on the Swahili coast , Dar es Salaam is an important economic center and one of the fastest-growing cities in the world. The town was founded by Majid bin Said ,

4773-412: Is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as reverse transcriptase , proteases , ribonuclease and integrase . A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle. This is, in turn, surrounded by the viral envelope , that is composed of the lipid bilayer taken from the membrane of

4902-545: Is undergoing major construction and development. The 35-storey PSPF Twin Towers are the second tallest building in the city and the country. The city has major infrastructural challenges, including an outdated transport system and occasional power rationing. The Dar es Salaam Stock Exchange (DSE) is the country's first stock market. The headquarters of the Natural Gas Revenue Fund is also here. Dar es Salaam hosts

5031-534: Is unknown how often such mixed packaging occurs under natural conditions. Bonhoeffer et al. suggested that template switching by reverse transcriptase acts as a repair process to deal with breaks in the single-stranded RNA genome. In addition, Hu and Temin suggested that recombination is an adaptation for repair of damage in the RNA genomes. Strand switching (copy-choice recombination) by reverse transcriptase could generate an undamaged copy of genomic DNA from two damaged single-stranded RNA genome copies. This view of

5160-633: The African green monkey (SIVagm) and sooty mangabey (SIVsmm) are thought to have a long evolutionary history with their hosts. These hosts have adapted to the presence of the virus, which is present at high levels in the host's blood, but evokes only a mild immune response, does not cause the development of simian AIDS, and does not undergo the extensive mutation and recombination typical of HIV infection in humans. In contrast, when these strains infect species that have not adapted to SIV ("heterologous" or similar hosts such as rhesus or cynomologus macaques ),

5289-541: The CCR5-Δ32 mutation are resistant to infection by the R5 virus, as the mutation leaves HIV unable to bind to this co-receptor, reducing its ability to infect target cells. Sexual intercourse is the major mode of HIV transmission. Both X4 and R5 HIV are present in the seminal fluid , which enables the virus to be transmitted from a male to his sexual partner . The virions can then infect numerous cellular targets and disseminate into

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5418-520: The Central Line from Dar es Salaam west to Kigoma . The city also hosts the head office of Tanzania–Zambia Railways Authority (TAZARA) built in the late 1960s to early 1970s. The main terminal is located west of Dar es Salaam's central business district in north Yombo Vituka along the Nelson Mandela Road. The TAZARA Railway connects Dar es Salaam to Zambia. Tanzania Standard Gauge Railway

5547-674: The Kisutu , Kivukoni , Upanga and Kariakoo areas. The downtown area is located in the Ilala district. Kivukoni is home to the Tanzania Central Bank, The Bank of Tanzania , the Dar es Salaam Stock Exchange and the city's important Magogoni fish market. With businesses and offices, Kisutu is the location of Dar es Salaam central railway station, the PSPF Towers, and the TPA Tower. Dar es Salaam

5676-658: The Mlimani City shopping mall, the City Mall in the Kisutu area, Quality Center Mall, GSM Pugu Shopping Mall, GSM Msasani Mall, and Dar Free Market Mall. On a natural harbour on the Indian Ocean, Dar es Salaam is one of the hubs of the Tanzanian transportation system , as the main railways and several highways originate in or near the city to provide convenient transportation for commuters. Public minibus share taxis ( dala dala ) are

5805-676: The Writer's Guild of Great Britain Award for Television Series Writing and the Aga Khan Award for Excellence in the Arts. He was selected as one of 2010's Breakthrough Brits on the prestigious UK Film Council ( BFI ) programme alongside Riz Ahmed , Yann Demange , Daniel Kaluuya and others. His film and TV career began when he won a place on the prestigious BBC internship scheme Black Screen , alongside writers such as playwright Tanika Gupta . In 2022, Ian

5934-445: The adsorption of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the target cell membrane and the release of the HIV capsid into the cell. Entry to the cell begins through interaction of the trimeric envelope complex ( gp160 spike) on the HIV viral envelope and both CD4 and a chemokine co-receptor (generally either CCR5 or CXCR4 , but others are known to interact) on

6063-421: The gag polyproteins still need to be cleaved into the actual matrix, capsid and nucleocapsid proteins. This cleavage is mediated by the packaged viral protease and can be inhibited by antiretroviral drugs of the protease inhibitor class. The various structural components then assemble to produce a mature HIV virion. Only mature virions are then able to infect another cell. The classical process of infection of

6192-658: The immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype . In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood , pre-ejaculate , semen , and vaginal fluids . Non-sexual transmission can occur from an infected mother to her infant during pregnancy , during childbirth by exposure to her blood or vaginal fluid, and through breast milk . Within these bodily fluids, HIV

6321-514: The microtubule -based transport to the nucleus, the viral single-strand RNA genome is transcribed into double-strand DNA, which is then integrated into a host chromosome. HIV can infect dendritic cells (DCs) by this CD4-CCR5 route, but another route using mannose-specific C-type lectin receptors such as DC-SIGN can also be used. DCs are one of the first cells encountered by the virus during sexual transmission. They are currently thought to play an important role by transmitting HIV to T cells when

6450-403: The phylogenetic tree representing the lineage of the M group of HIV-1. Co-infection with distinct subtypes gives rise to circulating recombinant forms (CRFs). In 2000, the last year in which an analysis of global subtype prevalence was made, 47.2% of infections worldwide were of subtype C, 26.7% were of subtype A/CRF02_AG, 12.3% were of subtype B, 5.3% were of subtype D, 3.2% were of CRF_AE, and

6579-438: The α -chemokine receptor, CXCR4 , for entry. Dual-tropic HIV-1 strains are thought to be transitional strains of HIV-1 and thus are able to use both CCR5 and CXCR4 as co-receptors for viral entry. The α -chemokine SDF-1 , a ligand for CXCR4, suppresses replication of T-tropic HIV-1 isolates. It does this by down-regulating the expression of CXCR4 on the surface of HIV target cells. M-tropic HIV-1 isolates that use only

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6708-427: The β -chemokine receptor, CCR5 , for entry and are thus able to replicate in both macrophages and CD4 T cells. This CCR5 co-receptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. Indeed, macrophages play a key role in several critical aspects of HIV infection. They appear to be the first cells infected by HIV and perhaps the source of HIV production when CD4 cells become depleted in

6837-467: The 1970s, the Ministry of National Youth Culture aimed to create a national culture stressing the importance of music. Dar es Salaam became the music center in Tanzania, with the local radio showcasing new bands and dominating the music and cultural scene. With this ujamaa (family) mentality governing culture and music, a unified people's culture was created, leading to the rise of hip hop culture. Throughout

6966-491: The 1980s, the policy failed to combat the increasing poverty and hunger that Tanzania faced, and had delayed necessary development. This situation led to the liberalization policy of the 1980s that essentially ended socialism and silenced its proponents within Tanzania's government through political repression. Until the late 1990s, Dar es Salaam was not regarded in the same echelon as Africa's leading cities like Cairo , Nairobi , Johannesburg , Lagos , or Addis Ababa . During

7095-480: The 2000s, businesses opened and prospered; growth expanded in the construction sector, with new multi-storey buildings, bridges and roads; Tanzanian banks headquartered in the city became better regulated ; and the Dar es Salaam Stock Exchange expanded. The port is prominent for entrepot trade with landlocked countries like Rwanda , Burundi , Zambia , and the eastern portion of the Democratic Republic of

7224-424: The 2022 IPCC Sixth Assessment Report , Dar es Salaam is one of 12 major African cities ( Abidjan , Alexandria , Algiers , Cape Town , Casablanca , Dakar , Dar es Salaam, Durban , Lagos , Lomé , Luanda and Maputo ) which would be the most severely affected by the future sea level rise . It estimates that they would collectively sustain cumulative damages of US$ 65 billion under RCP 4.5 and US$ 86.5 billion for

7353-537: The British Tanganyika Territory . Dar es Salaam remained the administrative and commercial centre. Under British indirect rule , European areas such as Oyster Bay and African areas (e.g., Kariakoo and Ilala ) developed separately from the city centre. The city's population also included a large number of workers from British India , many of whom came to take advantage of trade and commercial opportunities. After World War II, Dar es Salaam experienced

7482-583: The CCR5 receptor are termed R5; those that use only CXCR4 are termed X4, and those that use both, X4R5. However, the use of co-receptors alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection and HIV can also infect a subtype of myeloid dendritic cells , which probably constitute a reservoir that maintains infection when CD4 T cell numbers have declined to extremely low levels. Some people are resistant to certain strains of HIV. For example, people with

7611-524: The Congo . The city's skyline features tall buildings, among them the 35-storey PSPF Tower (finished in 2015) and the Tanzania Ports Authority (TPA) Tower, the tallest in the country (completed in 2016). A number of historical buildings and elements of urban planning, such as parts of the harbour and streets going back to colonial times, still exist. The Old Boma , one of the city's oldest buildings,

7740-405: The DIS (dimerization initiation signal) hairpin is exposed. The formation of the gRNA dimer is mediated by a 'kissing' interaction between the DIS hairpin loops of the gRNA monomers. At the same time, certain guanosine residues in the gRNA are made available for binding of the nucleocapsid (NC) protein leading to the subsequent virion assembly. The labile gRNA dimer has been also reported to achieve

7869-419: The HIV env gene, allows the virus to attach to target cells and fuse the viral envelope with the target cell's membrane releasing the viral contents into the cell and initiating the infectious cycle. As the sole viral protein on the surface of the virus, the envelope protein is a major target for HIV vaccine efforts. Over half of the mass of the trimeric envelope spike is N-linked glycans . The density

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7998-441: The HIV protein-coding sequences is translated. Mature HIV mRNAs are exported from the nucleus into the cytoplasm , where they are translated to produce HIV proteins, including Rev . As the newly produced Rev protein is produced it moves to the nucleus, where it binds to full-length, unspliced copies of virus RNAs and allows them to leave the nucleus. Some of these full-length RNAs function as mRNAs that are translated to produce

8127-570: The HIV virological synapse in vivo . The many dissemination mechanisms available to HIV contribute to the virus' ongoing replication in spite of anti-retroviral therapies. HIV differs from many viruses in that it has very high genetic variability . This diversity is a result of its fast replication cycle , with the generation of about 10 virions every day, coupled with a high mutation rate of approximately 3 x 10 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase. This complex scenario leads to

8256-516: The LTR promoter acting by binding the TAR RNA element. The TAR may also be processed into microRNAs that regulate the apoptosis genes ERCC1 and IER3 . The rev protein (p19) is involved in shuttling RNAs from the nucleus and the cytoplasm by binding to the RRE RNA element. The vif protein (p23) prevents the action of APOBEC3G (a cellular protein that deaminates cytidine to uridine in

8385-433: The U.S.: Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. In general, a second specimen should be collected more than a month later and retested for persons with indeterminate western blot results. Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations. In addition,

8514-409: The adaptive benefit of recombination in HIV could explain why each HIV particle contains two complete genomes, rather than one. Furthermore, the view that recombination is a repair process implies that the benefit of repair can occur at each replication cycle, and that this benefit can be realized whether or not the two genomes differ genetically. On the view that recombination in HIV is a repair process,

8643-423: The advent of AIDS. HIV-positive patients acquire an enormously broad spectrum of opportunistic infections, which was particularly problematic prior to the onset of HAART therapies; however, the same infections are reported among HIV-infected patients examined post-mortem following the onset of antiretroviral therapies. Thus, during the course of infection, viral adaptation to the use of CXCR4 instead of CCR5 may be

8772-403: The animals develop AIDS and the virus generates genetic diversity similar to what is seen in human HIV infection. Chimpanzee SIV (SIVcpz), the closest genetic relative of HIV-1, is associated with increased mortality and AIDS-like symptoms in its natural host. SIVcpz appears to have been transmitted relatively recently to chimpanzee and human populations, so their hosts have not yet adapted to

8901-592: The cell as new virus particles that will begin the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both lymphadenopathy associated virus (LAV) and human T-lymphotropic virus 3 (HTLV-III). HIV-1 is more virulent and more infective than HIV-2, and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2, compared to HIV-1, implies that fewer of those exposed to HIV-2 will be infected per exposure. Due to its relatively poor capacity for transmission, HIV-2

9030-470: The cell types a virus infects. HIV can infect a variety of immune cells such as CD4 T cells , macrophages , and microglial cells . HIV-1 entry to macrophages and CD4 T cells is mediated through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells' membrane and also with chemokine co-receptors . Macrophage-tropic (M-tropic) strains of HIV-1, or non- syncytia -inducing strains (NSI; now called R5 viruses ) use

9159-432: The city's central business district. Due to a huge influx of cargo and the slow pace of expansion, a new cargo port 60 km (37 mi) northwest of Dar es Salaam is proposed at Bagamoyo . MV Kigamboni ferries run between southeast of Kivukoni and northwest of Kigamboni in Dar es Salaam. Travel to urban and suburban parts of the city is provided by the Dar es Salaam commuter rail . Tanzania Railways operates

9288-580: The city's suburbs or wards. Kinondoni is the most populated of the districts. It houses half of the city's population and several high-income suburbs. The administrative district of Ilala contains almost all government offices, ministries, and the Central Business District. It is the transportation hub of the city, as the Julius Nyerere International Airport , Central Railway Station and Tazara Railway Station are all within

9417-454: The collapse of the extracellular portion of gp41 into a hairpin shape. This loop structure brings the virus and cell membranes close together, allowing fusion of the membranes and subsequent entry of the viral capsid. After HIV has bound to the target cell, the HIV RNA and various enzymes, including reverse transcriptase, integrase, ribonuclease, and protease, are injected into the cell. During

9546-528: The construction of the Central Railway Line in the early 1900s. In the East African campaign of World War I , British and Empire forces captured German East Africa . The Royal Navy bombarded the city with the monitor Mersey on 21 July 1916 and battleship HMS  Vengeance on 21 August. The German colonial authorities surrendered the city on 3 September. German East Africa became

9675-434: The country except for one. Dar es Salaam is the second-fastest-growing city in the world and could have a population as high as 12.9 million by 2030. The population was estimated at 20,000 in 1900, 93,000 in 1957 and 273,000 in 1967. Dar es Salaam is Tanzania's most important city for both business and government. The city contains high concentrations of trade and other services and manufacturing compared to other parts of

9804-585: The country, which has about 65 percent of its population in rural areas. Downtown includes small businesses, many of which are run by traders and proprietors whose families originated in the Middle East and the Indian subcontinent—areas of the world with which the settlements of the Tanzanian coast have had long-standing trading relations. The Dar es Salaam Central Business District is the largest in Tanzania and comprises

9933-415: The critical hit and Peabody Awards winning series Sort Of , which has appeared on many end-of-year best lists after it dropped on CBC and HBO Max in late 2021. For Sort Of , he has been nominated for best comedy series writer at the 10th Canadian Screen Awards and the 2022 Writers Guild of Canada award for the episode "Sort Of Mary Poppins". Rashid began working as a writer in UK television in

10062-447: The development of AIDS. HIV is a member of the genus Lentivirus , part of the family Retroviridae . Lentiviruses have many morphologies and biological properties in common. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period . Lentiviruses are transmitted as single-stranded , positive- sense , enveloped RNA viruses . Upon entry into

10191-577: The development of stable recombinant forms of the viral spike by the introduction of an intersubunit disulphide bond and an isoleucine to proline mutation ( radical replacement of an amino acid) in gp41. The so-called SOSIP trimers not only reproduce the antigenic properties of the native viral spike, but also display the same degree of immature glycans as presented on the native virus. Recombinant trimeric viral spikes are promising vaccine candidates as they display less non-neutralising epitopes than recombinant monomeric gp120, which act to suppress

10320-531: The district's boundaries. The residential areas are mainly middle- to high-income, among them: Temeke is the main industrial district of the city, where manufacturing (both heavy and light industry) is located. To the east is the Port of Dar es Salaam, the largest port in the country. Temeke is believed to have the largest concentration of low-income residents due to industry. It is home to military and police officers as well as port officials. The Ubungo terminal serves as

10449-520: The first Sultan of Zanzibar , in 1865 or 1866. It was the main administrative and commercial center of German East Africa , Tanganyika , and Tanzania. The decision was made in 1974 to move the capital to Dodoma which was officially completed in 1996. Dar es Salaam is Tanzania's most prominent city for arts, fashion, media, film, television, and finance. It is the capital of the co-extensive Dar es Salaam Region, one of Tanzania's 31 administrative regions , and consists of five districts : Kinondoni in

10578-431: The generation of many variants of HIV in a single infected patient in the course of one day. This variability is compounded when a single cell is simultaneously infected by two or more different strains of HIV. When simultaneous infection occurs, the genome of progeny virions may be composed of RNA strands from two different strains. This hybrid virion then infects a new cell where it undergoes replication. As this happens,

10707-576: The generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching. HIV-1 infection causes chronic inflammation and production of reactive oxygen species . Thus, the HIV genome may be vulnerable to oxidative damage , including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defense strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod et al. suggested that recombination by viruses

10836-552: The genetic information that is transmitted from parental to progeny genomes. Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-retroviral therapy . Recombination may also contribute, in principle, to overcoming the immune defenses of the host. Yet, for the adaptive advantages of genetic variation to be realized, the two viral genomes packaged in individual infecting virus particles need to have arisen from separate progenitor parental viruses of differing genetic constitution. It

10965-427: The high-emission scenario RCP 8.5 by the year 2050. Additionally, RCP 8.5 combined with the hypothetical impact from marine ice sheet instability at high levels of warming would involve up to US$ 137.5 billion in damages, while the additional accounting for the "low-probability, high-damage events" may increase aggregate risks to US$ 187 billion for the "moderate" RCP4.5, US$ 206 billion for RCP8.5 and US$ 397 billion under

11094-428: The high-end ice sheet instability scenario. Since sea level rise would continue for about 10,000 years under every scenario of climate change, future costs of sea level rise would only increase, especially without adaptation measures. In his 1979 journal A Modern History of Tanganyika , historian John Iliffe wrote, "In 1949 the town became a municipality...[with] four honourable nominated Town Councillors who elected

11223-524: The history of Tanzania; most notably, it exhibits some of the bones of Paranthropus boisei that were among the findings of Louis Leakey at Olduvai . In 2016, there was a breakthrough discovery in Northern Tanzania by a scientist, from the University of Dar es Salaam, of footprints thought to be of a hominid that predates Homo sapiens . The Makumbusho Cultural Centre & Village Museum, located in

11352-415: The immune response to target epitopes. The RNA genome consists of at least seven structural landmarks ( LTR , TAR , RRE , PE, SLIP, CRS, and INS), and nine genes ( gag , pol , and env , tat , rev , nef , vif , vpr , vpu , and sometimes a tenth tev , which is a fusion of tat , env and rev ), encoding 19 proteins. Three of these genes, gag , pol , and env , contain information needed to make

11481-518: The integrated DNA provirus is transcribed into RNA. The full-length genomic RNAs (gRNA) can be packaged into new viral particles in a pseudodiploid form. The selectivity in the packaging is explained by the structural properties of the dimeric conformer of the gRNA. The gRNA dimer is characterized by a tandem three-way junction within the gRNA monomer, in which the SD and AUG hairpins , responsible for splicing and translation respectively, are sequestered and

11610-739: The late 1990s, trained on the BBC 's Black Screen internship. His early credits include Dilly Downtown , and the soap London Bridge (Carlton Television for ITV) along with the BAFTA and Royal Television Society award winner, This Life . For BBC 's Woman's Hour Programme , Rashid wrote and directed Leaving Normal , a comedy serial about same-sex adoption starring Imelda Staunton and Meera Syal . Since then, Rashid has written for broadcasters and companies such as Showtime , Lionsgate , Amazon Prime Video , ITV (TV network) and Sphere Media . Most recently, he served as co-executive producer and writer on

11739-481: The most common form of transport in Dar es Salaam and are often found at the major bus terminals of Makumbusho , Ubungo and other areas of the city. However, since the introduction of the motorcycle transit business known as "bodaboda", most people prefer it, allowing them to get into the city faster as compared with the minibuses, which encounter heavy traffic. Other types of transport include motorcycles and bajaj (auto rickshaws). The government has been introducing

11868-464: The north; Ilala in the centre; Ubungo and Temeke in the south; and Kigamboni in the east across the Kurasini estuary. In the 19th century, Mzizima ( Swahili for "healthy town") was a coastal fishing village on the periphery of Indian Ocean trade routes . In 1865 or 1866, Sultan Majid bin Said of Zanzibar began building a new city very close to Mzizima and named it Dar es Salaam. The name

11997-568: The outskirts of the city on the road to Bagamoyo, showcases traditional huts from 16 different Tanzanian ethnic groups. There are also examples of traditional cultivation, as well as daily traditional music and dance shows. Close to the National Museum are also the botanical gardens , with tropical plants and trees. There are beaches on the Msasani peninsula north of Dar es Salaam and in Kigamboni to

12126-410: The patient. Macrophages and microglial cells are the cells infected by HIV in the central nervous system . In the tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce huge amounts of virus. T-tropic strains of HIV-1, or syncytia -inducing strains (SI; now called X4 viruses ) replicate in primary CD4 T cells as well as in macrophages and use

12255-404: The population was estimated to be 7.3 million. When the 2012 national census was taken, the city had a population of 4,364,541, about ten percent of the country's total. The average private household size was 3.9 persons compared to the national average of 4.7. Less than half of the city's residents were married, with a rate lower than any other region in the country. The literacy rate in the city

12384-406: The remaining 5.3% were composed of other subtypes and CRFs. Most HIV-1 research is focused on subtype B; few laboratories focus on the other subtypes. The existence of a fourth group, "P", has been hypothesised based on a virus isolated in 2009. The strain is apparently derived from gorilla SIV (SIVgor), first isolated from western lowland gorillas in 2006. HIV-2's closest relative is SIVsm,

12513-425: The reverse transcriptase, by jumping back and forth between the two different RNA templates, will generate a newly synthesized retroviral DNA sequence that is a recombinant between the two parental genomes. This recombination is most obvious when it occurs between subtypes. The closely related simian immunodeficiency virus (SIV) has evolved into many strains, classified by the natural host species. SIV strains of

12642-422: The same period, Ocean Road Hospital also belongs to a number of early historical buildings in Dar es Salaam. Dar es Salaam is located at 6°48' S, 39°17' E (−6.8000, 39.2833), on a natural harbour on the coast of East Africa, with sandy beaches in some areas. Dar es Salaam Region is divided into five administrative districts, four of which are governed by municipal councils that are affiliated with

12771-516: The single-stranded viral DNA and/or interferes with reverse transcription ). The vpr protein (p14) arrests cell division at G2/M . The nef protein (p27) down-regulates CD4 (the major viral receptor), as well as the MHC class I and class II molecules. Nef also interacts with SH3 domains . The vpu protein (p16) influences the release of new virus particles from infected cells. The ends of each strand of HIV RNA contain an RNA sequence called

12900-412: The site of cell-to-cell contact, close apposition of cells, which minimizes fluid-phase diffusion of virions, and clustering of HIV entry receptors on the target cell towards the contact zone. Cell-to-cell spread is thought to be particularly important in lymphoid tissues , where CD4 T cells are densely packed and likely to interact frequently. Intravital imaging studies have supported the concept of

13029-583: The south. Bongoyo Island can be reached by boat from the Msasani Slipway. The city is home to several churches and mosques . The churches in the city belong to various denominations; for example, Roman Catholic Archdiocese of Dar es Salaam ( Catholic Church ), Anglican Church of Tanzania ( Anglican Communion ), Evangelical Lutheran Church in Tanzania ( Lutheran World Federation ), Baptist Convention of Tanzania ( Baptist World Alliance ), Ilala Seventh Day Adventist Church and Assemblies of God . There

13158-673: The specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., a polymerase chain reaction (PCR), western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or PCR or reactive by western blot are considered HIV-positive and indicative of HIV infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate western blot result, which may be either an incomplete antibody response to HIV in an infected person or nonspecific reactions in an uninfected person. HIV deaths in 2014 excluding

13287-553: The structural proteins Gag and Env. Gag proteins bind to copies of the virus RNA genome to package them into new virus particles. HIV-1 and HIV-2 appear to package their RNA differently. HIV-1 will bind to any appropriate RNA. HIV-2 will preferentially bind to the mRNA that was used to create the Gag protein itself. Two RNA genomes are encapsidated in each HIV-1 particle (see Structure and genome of HIV ). Upon infection and replication catalyzed by reverse transcriptase, recombination between

13416-496: The structural proteins for new virus particles. For example, env codes for a protein called gp160 that is cut in two by a cellular protease to form gp120 and gp41. The six remaining genes, tat , rev , nef , vif , vpr , and vpu (or vpx in the case of HIV-2), are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus (replicate), or cause disease. The two tat proteins (p16 and p14) are transcriptional transactivators for

13545-427: The target cell surface. Gp120 binds to integrin α 4 β 7 activating LFA-1 , the central integrin involved in the establishment of virological synapses , which facilitate efficient cell-to-cell spreading of HIV-1. The gp160 spike contains binding domains for both CD4 and chemokine receptors. The first step in fusion involves the high-affinity attachment of the CD4 binding domains of gp120 to CD4. Once gp120

13674-413: The target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded enzyme, reverse transcriptase , that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded enzyme, integrase , and host co-factors . Once integrated,

13803-522: The third season of Sort Of , for the Canadian Broadcasting Corporation and HBO Max . The Canadian series won many awards nationally and internationally including at the 2022 Peabody Awards . He is currently developing Nobel Prize laureate Abdulrazak Gurnah 's novel Afterlives into a series for Razor Film and Warp Films . He also has projects in development with Crave and the Canadian Broadcasting Corporation . In 2022, Ian

13932-414: The two HIV envelope glycoproteins, gp41 and gp120 . These are transported to the plasma membrane of the host cell where gp41 anchors gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. The budded virion is still immature as

14061-484: The two genomes can occur. Recombination occurs as the single-strand, positive-sense RNA genomes are reverse transcribed to form DNA. During reverse transcription, the nascent DNA can switch multiple times between the two copies of the viral RNA. This form of recombination is known as copy-choice. Recombination events may occur throughout the genome. Anywhere from two to 20 recombination events per genome may occur at each replication cycle, and these events can rapidly shuffle

14190-570: The viral DNA into the host cell's genome is carried out by another viral enzyme called integrase . The integrated viral DNA may then lie dormant, in the latent stage of HIV infection. To actively produce the virus, certain cellular transcription factors need to be present, the most important of which is NF- κ B (nuclear factor kappa B), which is upregulated when T cells become activated. This means that those cells most likely to be targeted, entered and subsequently killed by HIV are those actively fighting infection. During viral replication,

14319-536: The virus in its adaptation to avoid innate restriction factors present in host cells. Adaptation to use normal cellular machinery to enable transmission and productive infection has also aided the establishment of HIV-2 replication in humans. A survival strategy for any infectious agent is not to kill its host, but ultimately become a commensal organism. Having achieved a low pathogenicity, over time, variants that are more successful at transmission will be selected. The HIV virion enters macrophages and CD4 T cells by

14448-425: The virus is captured in the mucosa by DCs. The presence of FEZ-1 , which occurs naturally in neurons , is believed to prevent the infection of cells by HIV. HIV-1 entry, as well as entry of many other retroviruses, has long been believed to occur exclusively at the plasma membrane. More recently, however, productive infection by pH -independent, clathrin-mediated endocytosis of HIV-1 has also been reported and

14577-463: The virus may become latent , allowing the virus and its host cell to avoid detection by the immune system, for an indeterminate amount of time. The virus can remain dormant in the human body for up to ten years after primary infection; during this period the virus does not cause symptoms. Alternatively, the integrated viral DNA may be transcribed , producing new RNA genomes and viral proteins, using host cell resources, that are packaged and released from

14706-403: The virus to evade the body's immune system. The reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that creates a sense DNA from the antisense cDNA. Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus . The integration of

14835-537: The virus. This virus has also lost a function of the nef gene that is present in most SIVs. For non-pathogenic SIV variants, nef suppresses T cell activation through the CD3 marker. Nef 's function in non-pathogenic forms of SIV is to downregulate expression of inflammatory cytokines , MHC-1 , and signals that affect T cell trafficking. In HIV-1 and SIVcpz, nef does not inhibit T-cell activation and it has lost this function. Without this function, T cell depletion

14964-475: The whole organism. However, a selection process leads to a predominant transmission of the R5 virus through this pathway. In patients infected with subtype B HIV-1, there is often a co-receptor switch in late-stage disease and T-tropic variants that can infect a variety of T cells through CXCR4. These variants then replicate more aggressively with heightened virulence that causes rapid T cell depletion, immune system collapse, and opportunistic infections that mark

15093-447: The world of step dancing. It was nominated for a Sundance World Cinema Grand Jury Prize and purchased by Paramount Vantage. The film opened to positive reviews and strong box office. Rashid published his first poetry collection, Black Markets, White Boyfriends and Other Acts of Elision , in 1991. Two more followed: the chapbook Song of Sabu in 1993 and The Heat Yesterday in 1995. Rashid has recently started publishing poetry again, and

15222-496: The writer, curator, and academic Peter Ride . He then won a bursary to attend a prestigious BBC writing internship programme Black Screen and soon after started working in film and television as a screenwriter, director and producer. He currently divides his time between Canada and the UK. Rashid is best known for the iconic BAFTA -winning BBC show, This Life for which he won a Writer's Guild of Great Britain award, and for writing and co-exec producing across three seasons of

15351-521: The year 2050 would most closely resemble the current climate of Barquisimeto in Venezuela . The annual temperature and temperatures of the warmest month would increase by 1.3 °C (2.3 °F), while the temperature of the coldest month would go down by 0.1 °C (0.18 °F). According to Climate Action Tracker , the current warming trajectory appears consistent with 2.7 °C (4.9 °F), which closely matches RCP 4.5. Moreover, according to

15480-405: The year as 1968. In the early 1970s, his family was forced to leave Tanzania. After failing to secure asylum in the UK and US, they settled in Toronto. Rashid began his career as an arts journalist, critic, curator, and events programmer, particularly focussed on South Asian diasporic, Muslim and LGBTQ cultural work. In the early 1990s, Rashid returned to London, Britain, where he met his partner,

15609-529: The years, the radio in Dar es Salaam has played a major role in the dissemination of music, because many people do not have television; cassettes are more common than CDs. Dar es Salaam has two of the five museums that make up the National Museum of Tanzania consortium, namely the National Museum proper and the Makumbusho Cultural Centre & Village Museum. The National Museum is dedicated to

15738-498: Was 96%, while the national average was 78%. Between the 2002 and 2012 censuses, the city's 5.6% average annual growth rate was the highest in the country. More than three-quarters of the city's population live in informal settlements . In 2018, Dar es Salaam scored 0.631 (medium category) on the Human Development Index (HDI). The city's HDI has increased every year since 1992, and it ranked higher than any other region in

15867-563: Was a regular contributor to the Canadian LGBT magazine Rites , and the cultural journals Fuse and TSAR Publications . In 1995, he was the Guest Editor for Rungh magazine's Queer Special Issue. His curatorial catalogue essay for "Beyond Destinations", a show he curated for Ikon Gallery in 1993, was reprinted in Rungh in December 2019. He was also assistant editor of Bazaar Magazine ,

15996-602: Was awarded a fellowship on the CBC-BIPOC TV & Film Showrunner Catalyst in partnership with the Canadian Film Centre as an emerging television/streaming showrunner . Self-taught as a filmmaker, in 1991, Rashid made the short film Bolo Bolo! with Kaspar Saxena. The film, part of an HIV/AIDS cable access series called Toronto Living With AIDS , resulted in the series being pulled from Rogers Television after complaints about sexually suggestive content, though it had

16125-630: Was awarded a fellowship on the CBC-BIPOC TV & Film Showrunner Catalyst in partnership with the Canadian Film Centre as an emerging television/streaming Show Runner. His poetry has been nominated for the Gerald Lampert Award . His work as a writer and executive producer on the show Sort Of earned him a nomination for a Peabody Award in 2022. Dar es Salaam Dar es Salaam ( / ˌ d ɑːr ɛ s s ə ˈ l ɑː m / ; from Arabic : دَار السَّلَام , romanized :  Dār as-Salām , lit.   'Abode of Peace')

16254-681: Was built in 1866–67 by Majid bin Said , sultan of Zanzibar , and enlarged under German rule. The Botanical Gardens now are close to the National Museum of Tanzania . The present-day State House goes back to Majid bin Said, and were the seat of the German and later the British colonial governments. Along with the Azania Front Lutheran Church , built between 1899 and 1902, and the Roman Catholic St. Joseph's Cathedral , constructed around

16383-508: Was funded by the World Bank , African Development Bank and the Tanzanian government. Dar es Salaam will have a metro system, currently undergoing a feasibility study conducted by Mota-Engil and Dar Rapid Transit Agency . The Port of Dar es Salaam is Tanzania's busiest, handling 90% of the country's cargo. It is located in the Kurasini administrative ward of Temeke District southeast of

16512-448: Was recently suggested to constitute the only route of productive entry. Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the positive-sense single-stranded RNA genome from the attached viral proteins and copies it into a complementary DNA (cDNA) molecule. The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow

16641-520: Was traditionally popular in Zanzibar has also found a niche. However, it remains small compared both to dance music and " Bongo Flava ", a broad category representing the Tanzanian take on hip hop and rhythm and blues that has quickly become the most popular locally produced music. The rap music scene is also present. Traditional music, which locally refers to tribal music, is still performed, but typically only on family-oriented occasions such as weddings. In

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