Daily Current Affairs

Scientists are using fruit flies to find clues to Huntington’s disease (GS Paper 2, Health)

Why in news?

• Every month, the medical genetics clinic in the Nizam’s Institute of Medical Sciences, Hyderabad, sees three or four people with Huntington’s disease.
• Recently, researchers from the University of Szeged, in Hungary, has taken some important strides in this direction based on the diminutive fruit fly.

 

Symptoms & progress:

• At first, Huntington’s disease patients have mild symptoms: forgetfulness, loss of balance, and clumsiness in performing simple tasks. The symptoms begin between the ages of 30 and 50, by when the patient might also have had children. The condition progressively worsens.
• The patient suffers mood swings, has difficulty in reasoning, shows abnormal and uncontrollable jerky movements, and experiences difficulty in speaking, swallowing, and walking.
• The patient eventually dies, but not before raising the spectre that one or more of their children will suffer the same fate. There is no cure.

 

Glutamine repeats:

• The patient’s misfortune is that they carry a mutated version of a gene called HTT. The HTT gene codes for a protein called huntingtin, or Htt.
• Nerve cells in the human body require the Htt protein for their normal functioning and survival. The mutated gene, however, encodes an abnormal Htt protein that instead destroys the neurons that regulate movement, thinking, and memory.
• The normal HTT gene contains a stretch of DNA that specifies the number of times the amino acid glutamine is repeated in the Htt protein. This number varies from 11 to 31.
• In the mutant versions of the HTT gene, this stretch is expanded to encode 35 or more repeats. Researchers have even found variants with more than 150 repeats.
• As the number of repetitions increase, the severity of Huntington’s disease increases and its debilitation begins at an earlier age.

 

Gene Mutation:

• Everyone has two copies of the HTT gene: one inherited from the father and one from the mother. The disease is triggered even if only one copy of the gene is mutated while the other is normal. That is, the mutant gene is said to be dominant to its normal counterpart.
• Some proteins other than Htt also have tracts of multiple glutamines. In a subset of these proteins, the DNA sequence that encodes the tract is larger in mutated versions of the gene. In Huntington’s disease, these mutants also can cause region-specific neuronal degeneration in the brain that leads to muscle control disorders, like spinocerebellar ataxia.
• There are many enzymes that can cut up proteins that have polyglutamine tracts to create shorter fragments containing the polyglutamines. These fragments are toxic because they interfere adversely with several cellular processes.
• Different neurons have exhibited a graded sensitivity to these fragments depending on the protein.
• In sum, genes with polyglutamine tracts are (potentially) bad news. And we neither know why some of these genes are expanded nor how exactly the short fragments cause neuronal degeneration.

 

Genetic Engineering:

• In the new study from Hungary, the researchers genetically engineered fruit flies (Drosophila melanogaster) to express the polyglutamine tract of a mutated humanHTT gene in their nervous system.
• To do this, they used a gene called Gal4 from baker’s yeast (Saccharomyces cerevisiae). Gal4 contains information with which cells manufacture a protein called Gal4p. This protein binds specifically to a short DNA sequence called the upstream activating sequence (UAS).
• In baker’s yeast, when Gal4p binds to UAS, it activates the expression of all the genes that come after (i.e. downstream), allowing the yeast to utilise the sugar galactose.

 

Link with fruit fly genome:

• The Gal4/UAS system also works in the fruit fly genome. When the DNA sequence for the Gal4p protein is placed downstream of a fly gene called elav, something curious happens: the Gal4p protein is expressed in all of the fly’s neurons – and only in the neurons.
• If the fly also carries the mutated HTT gene downstream of UAS, then the fly’s neuronal cells make the bad Htt protein, with its polyglutamine tract. Again, these proteins are made only in the neurons.
• In this way, the researchers were able to modify fruit flies so that their neurons produced Htt proteins that had 120 repeating units of glutamine. These flies displayed neuronal degeneration, an impaired ability to climb surfaces, and lower viability as well as longevity.
• The researchers had a ‘control’ group, with fruit flies whose neurons made proteins with 25 repeating glutamine units which is in the ‘normal’ range for human HTT. These flies were largely unaffected.
• Expressing the longer tract produced symptoms in the fruit flies resembling those of Huntington’s disease in humans whereas expressing the shorter tract did not.

 

The Yod1 gene

• With the two groups in hand, the researchers set about testing whether the pathogenesis resembling Huntington’s disease in the fruit flies was changed for better or for worse when they turned the expression of different genes up or down.
• The team investigated 32 genes and found that excessive expression of one, called Yod1, removed all of the disease-like effects in the flies, including the neurodegeneration, impediments to motor activity, and lower viability and longevity.
• The team also found ‘control’ flies that expressed only the short tracts in the Htt proteins, or which jointly expressed the short tract and the Yod1 gene, also showed no signs of neurodegeneration.
• In addition, the overexpression of Yod1 was also found to increase the expression of other genes involved in specific cellular processes.
• The researchers interpreted this to mean certain cellular processes could be part of a broader response by the fly to the cellular stress caused by the longer tract.

 

What’s next?

• The scientists will still need to establish that fruit flies that overexpress the human version of the Yod1 gene will also suppress the Huntington’s-like pathogenesis.
• If the human gene has an ameliorative effect in the fly, it will be reasonable to expect its overexpression could ameliorate Huntington’s disease in humans, too.

 

Cabinet approves the Migration and Mobility Agreement between India and Italy

(GS Paper 2, International Relation)

Why in news?

• The Union Cabinet has given its ex-post facto approval to the proposal of Ministry of External Affairs to sign and ratify the Migration and Mobility Agreement between India and Italy.

Details:

• It would enhance people-to-people contacts, foster mobility of students, skilled workers, business people and young professionals and strengthen cooperation on issues related to irregular migration between the two sides.
• It locks-in the current Italian visa regime including mechanisms for post study opportunities, internships, professional trainings assuring an advantage for India under the existing labour mobility pathways under the Flows Decree.

 

Key provisions:

• Indian students wishing to gather initial professional experience, after completing academic/vocational training in Italy may be granted temporary residence in Italy for up to 12 months.
• The Italian side has detailed provisions related to Professional Training, Extracurricular Internships and Curricular Internships which allow Indian students/trainees to gain experience in Italian skill/training standards.
• For workers, the Italian side has reserved a quota of 5000, 6000 and 7000 non seasonal Indian workers for 2023, 2024 and 2025 under the current Flows Decree (Total reserved quota stands at 12000 for non-seasonal workers).
• Additionally, the Italian side has reserved a quota of 3000, 4000 and 5000 seasonal Indian workers for 2023, 2024 and 2025 under current Flows Decree (Total reserved quota stands at 8000 for seasonal workers).

 

Flows Decree:

• Under the Flows Decree, Italian side has offered incremental re­served quotas for both seasonal and non-seasonal workers from 2023-2025.
• The Agreement also formalises joint working on fur­thering mobility pathways between India and Italy through agreements on Youth Mobility and Facilitation of Recruitment of Indian qualified professionals in the healthcare and medical services sectors which will be discussed under the Joint Working Group (JWG).

 

Monitoring:

• This Agreement will come into effect on the first day of the second month following the date of receipt of the last of the two notifications by which Parties shall have communicated to each other the completion of their internal procedures necessary for its entry into force and will remain into force for a period of 5 years.
• Unless terminated by any Participant, the Agreement will be automatically renewed for a similar successive period.
• The Agreement provides a formal mechanism for its monitoring through a JWG which would meet periodically, in virtual or physical mode as convenient, and oversee its implementation.
• The JWG would share relevant information, evaluate implementation of Agreement and discuss all appropriate proposals to support implementation as necessary.

 

PM JANMAN scheme for Particularly Vulnerable Tribal Groups

(GS Paper 2, Social Justice)

Context:

• The Pradhan Mantri Janjati Adivasi Nyaya Maha Abhiyan (PM JANMAN), aimed at providing PVTG households and habitations with basic facilities such as safe housing, clean drinking water and sanitation, improved access to education, health and nutrition, road and telecom connectivity, and sustainable livelihood opportunities.
• In addition, saturation will also be ensured for schemes like Pradhan Mantri Jan Arogya Yojana (PMJAY), Sickle Cell Disease Elimination, TB Elimination, 100% immunisation, PM Poshan, PM Jan Dhan Yojana, etc.
• This initiative is part of the Pradhan Mantri-PVTG Development Mission announced in India’s 2022-23 Union Budget, allocating Rs 15,000 crore over three years to develop them.

 

Who are PVTGs?

• In 1960-61, the Dhebar Commission identified disparities among Scheduled Tribes, leading to the creation of the “Primitive Tribal Groups” (PTG) category. In 2006, this category was renamed Particularly Vulnerable Tribal Groups (PVTGs).
• Initially identifying 52 groups, the category was expanded to include 75 groups in 22,544 villages across 18 states and one Union Territory of India, totalling about 28 lakh individuals.
• These groups, living mainly in Maharashtra, Madhya Pradesh, Chhattisgarh, Jharkhand, Odisha, Andhra Pradesh, and Tamil Nadu, are characterised by pre-agricultural lifestyles, low literacy, small or stagnant populations, and subsistence economies.
• Population sizes vary significantly, from under 1,000 in some groups, such as the Great Andamanese (around 50) and the Onge (around 100), to over 1 lakh in others, such as Maria Gond of Maharashtra and Saura in Odisha. Some tribes in central India, like Birhor, face stagnation, while the Onge and Andamanese are experiencing a decline.

 

What are the challenges in their development?

• PVTGs are severely marginalised due to their isolation, low population, and distinct socio-economic and cultural traits.
• They struggle with limited access to basic services, social discrimination, and vulnerability to displacement from development and natural disasters. They have little political representation, hindering their participation in decision-making.
• Mainstream society often overlooks their traditional knowledge and practices, and stereotypes about their backwardness are prevalent.
• They are also battling loss of traditional livelihoods and resource rights, lack of market knowledge for Non-Timber Forest Produce, and exploitation by middlemen, threatening their traditional occupations.

 

What schemes have been floated for them?

• The Centre and state governments have introduced several initiatives to support PVTGs.
• The PVTG Development Plan provides education, healthcare, and livelihood opportunities while preserving traditional knowledge.
• The Pradhan Mantri Janjatiya Vikas Mission (PMJVM) focuses on market linkages and Minor Forest Produce (MFP) procurement at Minimum Support Prices.
• Other significant schemes include the Pradhan Mantri Adi Adarsh Gram Yojana, Integrated Tribal Development Project (ITDP) and Tribal Sub-Plan (TSP), which collectively aim for the holistic development of tribal areas.
• Additional measures like Eklavya Model Residential Schools, land titles under the Forest Rights Act 2006, Support to Tribal Research Institute (STRI) scheme, the Scheduled Castes and Scheduled Tribes (Prevention of Atrocities) Act 1989, The Panchayats (Extension to Scheduled Areas) Act 1996, and direct recruitment through reservations further aid in education, self-governance, and protection against discrimination.
• However, challenges in implementation, such as resource limitations, lack of awareness, and unequal treatment among different PVTG groups have affected the effectiveness of these schemes.

 

What does PM-JANMAN do differently?

• Proper identification and recognition: The criteria for identifying PVTGs have been criticised for being outdated. Some PVTGs are not recognised as Scheduled Tribes in certain states, and the list containing repetitive names has led to confusion and exclusion.
• Participatory bottom-up approach: To help PVTGs effectively, the scheme abandons the ‘one-size-fits-all’ approach in favour of customised strategies that respect their unique needs and priorities. It actively involves PVTGs in decision-making, addressing land rights, social inclusion, and cultural preservation.
• Livelihood promotion: Providing skills training and resources, like land and credit, will help in sustainable livelihoods. Implementing the Forest Rights Act by granting land titles secures access to forest resources. Section 3(1)(e) of the FRA specifically supports the rights of primitive tribal groups and pre-agricultural communities.
• Health, nutrition and education: Outreach strategies like Mobile Medical Health Units will be crucial for providing healthcare in remote areas. These strategies need to be tailored for specific health issues like teenage pregnancies and oral health, and overcoming language and cultural barriers through sensitised healthcare workers or hiring those from within the community.
• Infrastructure development: The habitations of PVTGs often don’t meet the criteria for schemes such as the Pradhan Mantri Grameen Sadak Yojana, Pradhan Mantri Awas Yojana and Jal Jeevan Mission due to factors like population requirements or lack of surveys.